Forever in your prime

Getting the word out

2009-04-06T09:57:00.001-04:00

Look at the timeline for these articles:

2009-03-27: New Scientist

2009-01-01: Science Direct

2008-10-28: International Journal of Pharmaceutics

This is worrisome, as it is taking over 6 months for word of research to get out to the community. I’m not sure if it’s better for people in the research field, I don’t know if they can find out who’s doing what faster than the lay-person can, but someone needs to get this info online for free much faster than is currently being done so people can co-ordinate.

Aging 2008 Symposium at UCLA

2008-06-03T14:45:00.001-04:00

Methuselah Foundation Announces Aging 2008 at UCLA

Have you ever dreamed of climbing Mt. Everest – on your 125th birthday?

Los Angeles, CA (May 19, 2008) On Friday June 27th, leading scientists and thinkers in stem cell research and regenerative medicine will gather in Los Angeles at UCLA for Aging 2008 to explain how their work can combat human aging, and the sociological implications of developing rejuvenation therapies.

Aging 2008 is free, with advance registration required at http://www.mfoundation.org/Aging2008/.

Dr. Aubrey de Grey, chairman and chief science ofﬁcer of the Methuselah Foundation, said "Our organization has raised over $10 million to crack open the logjams in longevity science. With the two-armed strategy of direct investments into key research projects, and a competitive prize to spur on scientists racing to break rejuvenation and longevity records in lab mice, the Foundation is actively accelerating the drive toward a future free of age-related degeneration." The Methuselah Foundation has been covered by 60 Minutes, Popular Science, The Wall Street Journal, and other top-ﬂight media outlets.

The State of California is a frontrunner in regenerative medicine and stem cell research. On November 2, 2004, more than seven million Californians voted to pass Proposition 71, establishing the California Institute for Regenerative Medicine, and allocating $3 billion over ten years to fund stem cell research. Proposition 71 was a rare instance of voters directly authorizing funding for scientiﬁc research.

The speakers at Aging 2008 will argue that the near-term consequences of intense research into regenerative medicine could be the development of therapies that extend healthy human life by decades, even if the therapies are applied in middle age. Peter Thiel, president of Clarium Capital, initial investor in Facebook, and lead sponsor of Aging 2008, said, "The time has come to challenge the inevitability of aging. This forum will provide an excellent opportunity to look at the scientiﬁc barriers that must be overcome to substantially extend healthy human life, as well as the ethical implications of doing so."

Aging 2008 also serves as the free opening session for the technically focused Understanding Aging Conference, which will run at UCLA on June 28th and 29th.

What: Aging: The Disease, The Cure, The Implications, hosted by Methuselah Foundation
When: Friday, June 27, 2008, Drinks 4pm, Presentations 5pm, Dinner 8pm
Where: Royce Hall, 405 Hilgard Ave, Los Angeles, CA 90024
Who:

§ Dr. Bruce Ames, Professor of Biochemistry and Molecular Biology at UC Berkeley

§ G. Steven Burrill, Chairman of Pharmasset and Chairman of Campaign for Medical Research

§ Dr. Aubrey de Grey, Chairman and CSO of Methuselah Foundation and author of Ending Aging

§ Dr. William Haseltine, Chairman of Haseltine Global Health

§ Daniel Perry, Executive Director of Alliance for Aging Research

§ Bernard Siegel, Executive Director of Genetics Policy Institute

§ Dr. Gregory Stock, Director of Program on Medicine, Technology & Society at UCLA School of Medicine

§ Dr. Michael West, CEO of BioTime and Adjunct Professor of Bioengineering at UC Berkeley

About Methuselah Foundation

The Methuselah Foundation is a 501(c)(3) nonproﬁt organization dedicated to extending the healthy human lifespan. Founded in 2002 by entrepreneur David Gobel and gerontologist Dr. Aubrey de Grey, the Methuselah Foundation funds two major projects: the Mprize, a multimillion dollar research prize, and SENS, a detailed engineering plan to repair aging-related damage. Learn more at http://mfoundation.org.

Media Contact: Maria Entraigues, 310-242-3660, mailto:maria@mfoundation.org

Universal Flue Vaccine Tested Successfully

2008-02-06T19:41:00.000-05:00

http://www.sciencedaily.com/releases/2008/01/080124185522.htm
ScienceDaily (Jan. 25, 2008)
The British-American biotech company Acambis reports the successful
conclusion of Phase I trials of the universal flu vaccine in humans. The
universal influenza vaccine has been pioneered by researchers from VIB and
Ghent University. This vaccine is intended to provide protection against all
'A' strains of the virus that causes human influenza, including pandemic
strains. Therefore, this vaccine will not need to be renewed annually.

10-Fold Life Span Extension Reported

2008-01-16T14:50:00.001-05:00

01/14/08
Record longevity for baker's yeast suggests strategies for helping humans
live longer and healthier, says USC study leader Valter Longo.
By Carl Marziali

Longo's group next plans to further investigate life span extension in mice.

Photo/S. Peter LopezBiologists have created baker's yeast capable of living
to 800 in yeast years without apparent side effects.

The basic but important discovery, achieved through a combination of dietary
and genetic changes, brings science closer to controlling the survival and
health of the unit of all living systems: the cell.

"We're setting the foundation for reprogramming healthy life," said USC
study leader Valter Longo.

The study is scheduled to appear in the Jan. 25 issue of the journal PLoS
Genetics. A companion study, showing that the same genetic changes in yeast
reverse the course of an accelerated aging syndrome, appears in the Jan. 14
issue of the Journal of Cell Biology.

Longo's group put baker's yeast on a calorie-restricted diet and knocked out
two genes, RAS2 and SCH9, that promote aging in yeast and cancer in humans.

"We got a 10-fold life span extension that is, I think, the longest one that
has ever been achieved in any organism," Longo said. In 2005, the same
research group reported a five-fold life span extension in the journal Cell.
Normal yeast organisms live about a week.

"I would say 10-fold is pretty significant," said Anna McCormick, chief of
the genetics and cell biology branch at the National Institute on Aging and
Longo's program officer.

The NIA funds such research in the hope of extending healthy life span in
humans through the development of drugs that mimic the life-prolonging
techniques used by Longo and others, McCormick added.

Baker's yeast is one of the most studied and best understood organisms at
the molecular and genetic level. Remarkably, in light of its simplicity,
yeast has led to the discovery of some of the most important genes and
pathways regulating aging and disease in mice and other mammals.

A study recently published in Cell (Issue 130, pages 247-258, 2007) reported
that a mouse with a gene mutation first identified by Longo's group lived 30
percent longer than normal and also was protected against heart and bone
diseases without apparent side effects.

Longo's group next plans to further investigate life span extension in mice
and also is studying a human population in Ecuador with mutations analogous
to those described in yeast.

"People with two copies of the mutations have very small stature and other
defects," he said. "We are now identifying the relatives with only one copy
of the mutation, who are apparently normal. We hope that they will show a
reduced incidence of diseases and an extended life span."

Longo cautioned that, as in the Ecuador case, longevity mutations tend to
come with severe growth deficits and other health problems. Finding drugs to
extend the human life span without side effects will not be easy, he said.

An easier goal, Longo added, would be to use the knowledge gained about life
span "in a fairly limited way, to reprogram disease prevention."

In the study appearing in the Jan. 14 Journal of Cell Biology, Longo's group
developed a yeast model for human Werner/Bloom syndromes, incurable diseases
that prematurely age, increase cancer incidence and eventually kill their
victims.

The same mutations that play a central role in the 10-fold life span
extension reversed the premature aging process, the researchers found.

Longo suggested that although a very simple system was used in his studies,
existing drugs targeting analogous anti-aging pathways in humans -
specifically the pathway involving Insulin Growth Factor, or IGF-1 - should
be considered for testing on Werner/Bloom patients.

"Maybe it will do nothing, but having nothing else, I think it's certainly a
good thing to try," Longo said.

In the PLoS Genetics study, Longo's group identified a major overlap between
the genes previously implicated in life span regulation for yeast and
mammals and those involved in life span extension under calorie restriction.

"We identified three transcription factors . that are very important for the
effect of calorie restriction, but at the same time, we also showed that
it's not enough because even without these transcription factors, calorie
restriction can still extend life span a little bit," Longo said.

"So that means that we've identified a lot of the key players in the calorie
restriction effect but not all of them."

Calorie restriction - in practice, controlled starvation - has long been
shown to reduce disease and extend life span in species from yeast to mice.

Scientists believe that a nutrient shortage kicks organisms into a
maintenance mode, enabling them to redirect energy from growth and
reproduction into anti-aging systems until the time they can feed and breed
again.

Calorie restriction is now being tested by other researchers on primates and
even humans, Longo said.

Longo has been studying aging at the cellular level for 15 years and has
published articles in the nation's leading scientific journals. His
laboratory developed a simple and inexpensive method for measuring the true
chronological life span of yeast. Previously, scientists used the number of
a yeast cell's offspring as a proxy for its age.

The so-called replicative life span technique remains in use, and the NIA's
McCormick said that Longo's method was controversial at first. However, she
said, the scientific community now appears to accept its usefulness. She
said Longo's "stationary phase" method is particularly applicable to studies
of cells that do not divide for most of their life, such as those in the
brain or in muscle.

"Stationary phase I think of as normal cell survival," McCormick said. She
added that NIA funds both stationary phase and replicative life span
research.

Longo is the Albert L. and Madelyne G. Hanson Family Trust Associate
Professor in Gerontology with a joint appointment as associate professor of
biological sciences at USC College. A native of Italy, Longo came to the
United States to study jazz performance but switched his major to
biochemistry as an undergraduate at the University of North Texas. He earned
his Ph.D. in biochemistry from UCLA in 1997 and completed his postdoctoral
training in neurobiology at USC.

The studies were funded by NIA (part of the National Institutes on Health)
and the American Federation for Aging Research.

USC graduate students Min Wei and Paola Fabrizio were first authors on the
PLoS Genetics paper. USC graduate students Federica Madia and Cristina
Gattazzo were first authors on the Journal of Cell Biology paper.

The other members of Longo's group were USC graduate students Abdoulaye
Galbani, Jesse Smith, Christopher Nguyen, Selina Huey, Lucio Comai, Jia Hu,
Huanying Ge and Chao Cheng, USC computational biologist Lei Li, and William
Burhans and Martin Weinberger of the Roswell Park Cancer Institute in
Buffalo, N.Y.

Reversing skin aging

2007-12-26T11:49:00.000-05:00

STANFORD, Calif. — Researchers at the Stanford University School of Medicine have reversed the effects of aging on the skin of mice, at least for a short period, by blocking the action of a single critical protein.The work could one day be useful in helping older people heal from an injury as quickly as they did when they were younger, said senior author Howard Chang, MD, PhD, assistant professor of dermatology. However, Chang and his colleagues warned their finding will likely be useful in short-term therapies in older people but not as a potential fountain of youth.The work backs up the theory that aging is the result of specific genetic changes rather than accumulated wear and tear, Chang said. What’s more, those genetic changes can be reversed even late in life.“The implication is that the aging process is plastic and potentially amenable to intervention,” Chang said. The results will be published in the Dec. 15 issue of the journal Genes and Development.The work came about thanks to existing data from experiments using microarrays, which detect the activity of all genes in a cell. In past experiments, researchers have found a large number of diverse genes that become either more active or less active in older people.Chang and graduate student Adam Adler, the study’s first author, searched through this existing data to see if those age-related genes had anything in common. It turned out that their activity gets dialed up or down with the help of the protein called NF-kappa-B.Chang said people had long known that NF-kappa-B winds its way into a cell’s nucleus to control which genes were active. What they didn’t know is that many of those genes regulated by the protein have a role in aging.Chang and Adler tested whether blocking the activity of NF-kappa-B in the skin of older mice for two weeks had a youthful effect. “We found a pretty striking reversal to that of the young skin,” Chang said.First they looked at the genetic changes resulting from blocking NF-kappa-B. After two weeks, the skin of 2-year-old mice had the same genes active as cells in the skin of newborn mice—a striking difference when compared with the skin of a normal 2-year-old mouse. The skin looked more youthful too. It was thicker and more cells appeared to be dividing, much like the skin of a younger mouse.Chang and Adler caution that their findings aren’t likely to be the source of the long-sought fountain of youth. That’s because they don’t know if the rejuvenating effects of NF-kappa-B are long-lasting. Also, the protein has roles in cancer, the immune system and a range of other functions throughout the body. Suppressing the protein on a long-term basis could very well result in cancers or other diseases that undermine its otherwise youthful effect.“You might get a longer lifespan but at the expense of something else,” Chang said. Instead, the researchers believe their work could point to a way of helping older people heal more quickly after surgery or boost organ function during illness. These short-term applications aren’t as likely to risk side effects that could accompany blocking such a critical protein. The work was supported by grants from the American Cancer Society, the National Institutes of Health, the National Cancer Institute and the California Breast Cancer Research Program. Other Stanford researchers who participated in the work are graduate student Tiara Kawahara and Jennifer Zhang, PhD, who was a postdoctoral scholar.
By Amy Adams

New Artificial Skin

2007-07-02T18:47:00.001-04:00

Intercytex said the new skin - called ICX-SKN - appeared to incorporate itself much better with real tissue than any other skin substitutes tried in the past, which biodegrade in situ after a few weeks.

The researchers hope it might provide an alternative to skin grafts, which are often used for victims of serious burns and large wounds.

ICX-SKN is created from a matrix produced by the same skin cells that are responsible for synthesising new tissue in the body. Results show that the new skin had produced a closed and healed wound site after just 28 days.

Fixing mitochondrial mutation

2007-07-01T22:17:00.001-04:00

A step taken towards obviating the mitochondrial DNA:

The possibility of synthesizing mitochondrial DNA (mtDNA)-coded proteins in the cytosolic compartment, called allotopic expression, provides an attractive option for genetic treatment of human diseases caused by mutations of the corresponding genes. However, it is now appreciated that the high hydrophobicity of proteins encoded by the mitochondrial genome represents a strong limitation on their mitochondrial import when translated in the cytosol. Recently, we optimized the allotopic expression of a recoded ATP6 gene in human cells, by forcing its mRNA to localize to the mitochondrial surface. In this study, we show that this approach leads to a long-lasting and complete rescue of mitochondrial dysfunction of fibroblasts harboring the neurogenic muscle weakness, ataxia and retinitis Pigmentosa T8993G ATP6 mutation or the Leber hereditary optic neuropathy G11778A ND4 mutation. The recoded ATP6 gene was associated with the cis-acting elements of SOD2, while the ND4 gene was associated with the cis-acting elements of COX10. Both ATP6 and ND4 gene products were efficiently translocated into the mitochondria and functional within their respective respiratory chain complexes. Indeed, the abilities to grow in galactose and to produce adenosine triphosphate (ATP) in vitro were both completely restored in fibroblasts allotopically expressing either ATP6 or ND4. Notably, in fibroblasts harboring the ATP6 mutation, allotopic expression of ATP6 led to the recovery of complex V enzymatic activity. Therefore, mRNA sorting to the mitochondrial surface represents a powerful strategy that could ultimately be applied in human therapy and become available for an array of devastating disorders caused by mtDNA mutations.

Link between mouse and human stem cells

2007-06-27T18:00:00.001-04:00

Human embryonic stem cells are the source of every cell, tissue and organ in
the body. Scientists want to use them to find cures for diseases like
Parkinson's, cancer and diabetes, although critics say it is wrong to use
any embryo in this way.

Laboratory mice have long been a favourite model for human disease but
researchers have been frustrated by the fact that human and mouse stem cells
behave very differently.

Now scientists think they may have cracked the problem.

Two papers published in the journal Nature show that when mouse stem cells
are derived from the innermost cell layer -- or epiblast -- of a week-old
rodent embryo they are in many ways almost identical to human ones.

Super fruit fly may lead to healthier humans

2007-06-11T18:22:00.000-04:00

Super fruit fly may lead to healthier humans: "Super fruit fly may lead to healthier humans
Aging slowed with single protein -- Technique holds promise for new drugs

In a triumph for pests, scientists have figured out how to make the fruit fly live longer.

But humans still may get something out of the deal. As reported online in Nature Chemical Biology, the discovery that a single protein can inhibit aging holds implications for human longevity and for treatment of some of the world’s most feared diseases.

“This work is important for two reasons,” said study author Richard Roberts, associate professor of chemistry, chemical engineering and biology at the University of Southern California.

“First, it demonstrates that a single inhibitor can dramatically alter lifespan, a very complex trait. It is remarkable that you can alter it with a single genetic change.

“We don’t really need to make fruit flies live longer, but if we understand how to do this, our approach may have direct application to higher organisms, such as ourselves.”"

scientists develop tiny implantable biocomputers

2007-05-22T11:16:00.001-04:00

Molecular devices' remarkably precise scans of cellular activity could revolutionize medicine

CAMBRIDGE, Mass. -- Researchers at Harvard University and Princeton University have made a crucial step toward building biological computers, tiny implantable devices that can monitor the activities and characteristics of human cells. The information provided by these "molecular doctors," constructed entirely of DNA, RNA, and proteins, could eventually revolutionize medicine by directing therapies only to diseased cells or tissues.

The results will be published this week in the journal Nature Biotechnology.

"Each human cell already has all of the tools required to build these biocomputers on its own," says Harvard's Yaakov (Kobi) Benenson, a Bauer Fellow in the Faculty of Arts and Sciences' Center for Systems Biology. "All that must be provided is a genetic blueprint of the machine and our own biology will do the rest. Your cells will literally build these biocomputers for you."

Evaluating Boolean logic equations inside cells, these molecular automata will detect anything from the presence of a mutated gene to the activity of genes within the cell. The biocomputers' "input" is RNA, proteins, and chemicals found in the cytoplasm; "output" molecules indicating the presence of the telltale signals are easily discernable with basic laboratory equipment.

"Currently we have no tools for reading cellular signals," Benenson says. "These biocomputers can translate complex cellular signatures, such as activities of multiple genes, into a readily observed output. They can even be programmed to automatically translate that output into a concrete action, meaning they could either be used to label a cell for a clinician to treat or they could trigger therapeutic action themselves."

Benenson and his colleagues demonstrate in their Nature Biotechnology paper that biocomputers can work in human kidney cells in culture. Research into the system's ability to monitor and interact with intracellular cues such as mutations and abnormal gene levels is still in progress.

Benenson and colleagues including Ron Weiss, associate professor of electrical engineering at Princeton, have also developed a conceptual framework by which various phenotypes could be represented logically.

A biocomputer's calculations, while mathematically simple, could allow researchers to build biosensors or medicine delivery systems capable of singling out very specific types or groups of cells in the human body. Molecular automata could allow doctors to specifically target only cancerous or diseased cells via a sophisticated integration of intracellular disease signals, leaving healthy cells completely unaffected.

To Treat the Dead

2007-05-07T08:46:00.001-04:00

The new science of resuscitation is changing the way doctors think about heart attacks�and death itself.

By Jerry Adler
Newsweek

May 7, 2007 issue - Consider someone who has just died of a heart attack. His organs are intact, he hasn't lost blood. All that's happened is his heart has stopped beating�the definition of "clinical death"�and his brain has shut down to conserve oxygen. But what has actually died?
Story continues below ↓advertisement

As recently as 1993, when Dr. Sherwin Nuland wrote the best seller "How We Die," the conventional answer was that it was his cells that had died. The patient couldn't be revived because the tissues of his brain and heart had suffered irreversible damage from lack of oxygen. This process was understood to begin after just four or five minutes. If the patient doesn't receive cardiopulmonary resuscitation within that time, and if his heart can't be restarted soon thereafter, he is unlikely to recover. That dogma went unquestioned until researchers actually looked at oxygen-starved heart cells under a microscope. What they saw amazed them, according to Dr. Lance Becker, an authority on emergency medicine at the University of Pennsylvania. "After one hour," he says, "we couldn't see evidence the cells had died. We thought we'd done something wrong." In fact, cells cut off from their blood supply died only hours later.

But if the cells are still alive, why can't doctors revive someone who has been dead for an hour? Because once the cells have been without oxygen for more than five minutes, they die when their oxygen supply is resumed. It was that "astounding" discovery, Becker says, that led him to his post as the director of Penn's Center for Resuscitation Science, a newly created research institute operating on one of medicine's newest frontiers: treating the dead.

Original Article

A good night's sleep with the flip of a switch?

2007-05-07T08:14:00.001-04:00

The flip of a switch could become all it takes to get a good night's sleep, according to a study released Monday. Researchers at the University of Wisconsin-Madison have found a way to stimulate the slow waves typical of deep sleep by sending a harmless magnetic signal through the skulls of sleeping volunteers.

Sleep remains one of the big mysteries in biology. All animals sleep, and people who are deprived of sleep suffer physically, emotionally and intellectually. But nobody knows how sleep restores the brain.

Now, Giulio Tononi, a professor of psychiatry at the University of Wisconsin-Madison School of Medicine and Public Health, has discovered how to stimulate brain waves that characterize the deepest stage of sleep. The discovery could open a new window into the role of sleep in keeping humans healthy, happy and able to learn. The study was published in the April 30 edition of the Proceedings of the National Academy of Sciences.

The brain function in question, called slow wave activity, is critical to the restoration of mood and the ability to learn, think and remember, Tononi says.

During slow wave activity, which occupies about 80 percent of sleeping hours, waves of electrical activity wash across the brain, roughly once a second, 1,000 times a night. In a paper being published this week in the Early Edition of the scientific journal PNAS, Tononi and colleagues, including Marcello Massimini, also of the UW-Madison School of Medicine and Public Health, described the use of transcranial magnetic stimulation (TMS) to initiate slow waves in sleeping volunteers. The researchers recorded brain electrical activity with an electroencephalograph (EEG).

A TMS instrument sends a harmless magnetic signal through the scalp and skull and into the brain, where it activates electrical impulses. In response to each burst of magnetism, the subjects' brains immediately produced slow waves typical of deep sleep, Tononi says. "With a single pulse, we were able to induce a wave that looks identical to the waves the brain makes normally during sleep."

Original Article

Breakthrough in regenerative medicine

2007-05-03T14:00:00.001-04:00

Findings described in a new study by Stanford scientists may be the first step toward a major revolution in human regenerative medicine�a future where advanced organ damage can be repaired by the body itself. In the May 2007 issue of The FASEB Journal, researchers show that a human evolutionary ancestor, the sea squirt, can correct abnormalities over a series of generations, suggesting that a similar regenerative process might be possible in people.

Missing limbs, scarred hearts, broken spines, and wounded muscles always try to repair themselves, but often the result is invalidism or disease. Even some tumors try to revert to normal, but are unsuccessful. If the genetic sequence described in the sea squirt applies to humans, this study represents a major step for regenerative medicine.

Original Article

Daily pill to beat genetic diseases

2007-05-02T14:38:00.001-04:00

A pill that can correct a wide range of faulty genes which cause crippling illnesses should be available within three years, promising a revolution in the treatment of thousands of conditions.

The drug, known as PTC124, has already had encouraging results in patients with Duchenne muscular dystrophy and cystic fibrosis. The final phase of clinical trials is to begin this year, and it could be licensed as early as 2009.

Original Article

Edmonton Aging Symposium

2007-04-22T09:06:00.001-04:00

Audio and video from the most recent Edmonton Aging Symposium is now online
at http://www.edmontonagingsymposium.com/index.php?pagename=eas_archive.
The content is hosted on Methuselah Foundation hardware, so please do your
part to help take the load off the servers by posting these videos to Google
Video, YouTube, or other video sharing sites. There is already one that I
know is up on google video, the debate between Gregory Stock and Daniel
Callahan, which was moderated by Aubrey de Grey is at
http://video.google.com/videoplay?docid=-8994837371721694774

Nanotech and biology

2007-04-22T08:44:00.001-04:00

Curcumin, a yellow polyphenol extracted from the rhizome of turmeric
(Curcuma longa), has potent anti-cancer properties as demonstrated in a
plethora of human cancer cell line and animal carcinogenesis models.
Nevertheless, widespread clinical application of this relatively efficacious
agent in cancer and other diseases has been limited due to poor aqueous
solubility, and consequently, minimal systemic bioavailability.
Nanoparticle-based drug delivery approaches have the potential for rendering
hydrophobic agents like curcumin dispersible in aqueous media, thus
circumventing the pitfalls of poor solubility.
Nanocurcumin, unlike free curcumin, is readily dispersed in aqueous media.
Nanocurcumin demonstrates comparable in vitro therapeutic efficacy to free
curcumin against a panel of human pancreatic cancer cell lines, as assessed
by cell viability and clonogenicity assays in soft agar. Further,
nanocurcumin's mechanisms of action on pancreatic cancer cells mirror that
of free curcumin, including induction of cellular apoptosis, blockade of
nuclear factor kappa B (NFkappaB) activation, and downregulation of steady
state levels of multiple pro-inflammatory cytokines (IL-6, IL-8, and
TNFalpha).
Conclusions: Nanocurcumin provides an opportunity to expand the clinical
repertoire of this efficacious agent by enabling ready aqueous dispersion.
Future studies utilizing nanocurcumin are warranted in pre-clinical in vivo
models of cancer and other diseases that might benefit from the effects of
curcumin.

Building the Bionic Man

2007-04-05T11:06:00.001-04:00

Once the realm of science fiction, bionics is slowly but surely becoming a reality. Advances in medical prostheses and computer technology are making the dream of building a bionic human a reality.

Original Article

Ways to Lure Viruses to Their Death

2007-04-03T15:09:00.001-04:00

There are only a few basic ways to fight viruses. A vaccine can prime the immune system to attack them as soon as they invade the body. If a virus manages to establish itself, a doctor may be able to prescribe a drug to slow down its spread. And if all else fails, a doctor may quarantine a patient to head off an epidemic.

Now some scientists are exploring a fundamentally different strategy to fight viruses. They want to wipe them out by luring them to their destruction, like mice to mousetraps.

Original Article

Artificial lymph nodes successfully implanted into mice.

2007-03-23T11:11:00.001-04:00

A team from the RIKEN institute in Japan has successfully transplated artifical lymph nodes using a collagen created bioscaffold into mice, where the lymph nodes successfully attracted lymphocytes already circulating in the mouse, and organized them just as they are in normal lymph nodes. After the node was filled with antigen specific lymphocytes, the team then transplated it to a mouse with no functioning immune system, where the lymphocytes then spread from the artifical node to the mouses own lymph nodes. When injected with the specific antigen, the mouses transplanted immune system responded, producing lymphocytes to neutralize the antigen.

Orignal article

Making memories that last a lifetime

2007-03-23T10:55:00.001-04:00

Neurobiologists have discovered a mechanism by which the constantly changing brain retains memories�from that dog bite to that first kiss. They have found that the brain co-opts the same machinery by which cells stably alter their genes to specialize during embryonic development.

Original Article

How common viruses can turn cells cancerous

2007-03-05T07:55:00.000-05:00

Common viruses may play a bigger role in cancer than anyone thought.

It is well known that certain viruses can trigger specific cancers. Human papillomavirus, for example, causes around 93 per cent of cancers of the cervix. Now Dominik Duelli and Yuri Lazebnik at Cold Spring Harbor Laboratory in New York and colleagues have found evidence for how they might do it.

During tumour development, the chromosomes of affected cells often become wildly rearranged, but no one knew why. Duelli and Lazebnik suspected that cell fusion - when two or more cells unite by merging membranes - might be to blame. Several common viruses can initiate this process.

To test their idea, the researchers took human fibroblast cells with genes that made them more likely to turn into a tumour and infected them with a retrovirus that can cause fusion. Sure enough, fused cells had many more chromosomal abnormalities than unfused ones, and when transplanted into mice, only the fused cells produced tumours (Current Biology, DOI: 10.1016/j.cub.2007.01.049).

The team is now asking other cancer researchers to examine tumour samples for signs of cell fusion.

Original Article

Mice Cloned from Skin Cells

2007-02-13T07:47:00.001-05:00

Healthy and viable mice that survive until adulthood have, for the first time, been cloned from adult stem cells. Scientists from Rockefeller University, including Howard Hughes Medical Institute investigator Elaine Fuchs, used cells called keratinocyte stem cells, which represent a new model system for cloning. Keratinocytes come from the skin, making them a particularly attractive stem cell source because of their ready accessibility. One day, they could be used to tailor therapies, as well as to better understand and treat diseases.

Original Article

Links between cancer and aging

2007-02-12T15:11:00.001-05:00

Wielding a palette of chromosome paints, scientists at the Salk Institute for Biological Studies have taken a step closer to understanding the relationship between aging and cancer by visualizing chromosomes of cells from patients with a heritable premature aging disease known as Werner Syndrome.

In a study to be published in this week�s online edition of the Proceedings of the National Academy of Sciences researchers led by Jan Karlseder, Ph.D., assistant professor in Salk�s Regulatory Biology Laboratory, showed that rebuilding structures called telomeres, which are found at the tips of each chromosome, significantly blocks the type of genetic damage seen in cells of patients with Werner Syndrome.

Patients with Werner Syndrome manifest signs of aging, such as skin wrinkling, baldness, or hair graying, in their teens. Most die in their 40�s or 50�s due to a predisposition to diseases like cancer. �Cancer is almost always related to chromosomal instability,� explains Karlseder. �If telomeres are lost on individual chromosomes, then chromosomes are not protected and can fuse with other nonprotected chromosomes. Then when cells divide, chromosomes randomly break, leading to genome instability.�

Original Article

Carnegie Mellon Mechanical Engineering Researcher Proposes Development of Artificial Cells To Fight Disease

2007-02-12T14:55:00.001-05:00

PITTSBURGH�Carnegie Mellon University's Philip LeDuc predicts the use of artificially created cells could be a potential new therapeutic approach for treating diseases in an ever-changing world. Philip LeDuc

LeDuc, an assistant professor of mechanical and biomedical engineering, penned an article for the January edition of Nature Nanotechnology Journal about the efficacy of using man-made cells to treat diseases without injecting drugs. This idea was developed by a team of researchers from disciplines including biology, chemistry and engineering during an exciting conference organized by the National Academies and the Keck Foundation for developing new disease-fighting approaches for the future.

"Our proposal is to use naturally available molecules to create pseudo-cell factories where we create a super artificial cell capable of targeting and treating whatever is ailing the body. The human cell is like a bustling metropolis, and we aim to tap the energy and diversity of the processes in a human cell to help the body essentially heal itself," LeDuc said.

Because the cell is an amazingly efficient system already, LeDuc and his team of researchers plan to use its microscopic package of tightly organized parts to improve medical treatment in diseases that exist in the body.

According to LeDuc's journal article, the living cell operates much like a tiny industrial complex. His article proposes using the processes in a cell, such as the membrane, to create an enclosed functioning environment for a nanofactory. Then, by using other biologically inspired processes like molecular-binding and transport, the pseudo-cell can target, modify and deliver chemicals that the body needs to function properly.

In contrast to traditional drug-discovery ideas, where the product is delivered many times into the body, this journal article suggests using molecules that are already in the body and modifying these nanoscale systems to produce the biochemicals deficient in the body to help fight disease.

"Understanding both the nature of a cell as an independent unit and its role in the life processes of larger organisms is crucial in our quest to duplicate the molecular units which form the building blocks of the cell and its parts," LeDuc said. "We see this development of artificial cells as a building block for a variety of new and exciting therapeutic approaches."

Original Article

Explaining How Mitochondrial Aging Leads to Diabetes

2007-02-12T07:27:00.001-05:00

As we age, the mitochondrial �motors� that power our cells start to lose their horsepower. This drop-off in mitochondrial activity predisposes us to accumulate intracellular fat in muscle and liver cells, which can lead to insulin resistance and type 2 diabetes. A new study directed by Howard Hughes Medical Institute investigator Gerald I. Shulman has shown how changes in an enzyme known to be vital to the body's energy levels may lead to a decreasing ability to stave off diabetes as we get older.

�Type 2 diabetes is a major problem for us as we age,� says Shulman, pointing to the 40 percent of people over age 65 who suffer from type 2 diabetes or impaired glucose tolerance. Hoping to unravel how aging affects the components of the cell's energy production system, Shulman and colleagues at Yale University studied the effects of aging on the activity of AMP-activated protein kinase (AMPK).

Original Article

Man-made Proteins Could Be More Useful than Real Ones

2007-02-07T09:31:00.001-05:00

Researchers have constructed a protein out of amino acids not found in natural proteins, discovering that they can form a complex, stable structure that closely resembles a natural protein. Their findings could help scientists design drugs that look and act like real proteins but won't be degraded by enzymes or targeted by the immune system, as natural proteins are.

The researchers, led by Howard Hughes Medical Institute (HHMI) professor Alanna Schepartz, report their findings in the February 14, 2007, issue of the Journal of the American Chemical Society, published in advance online on January 19, 2007. Schepartz and her coauthors, Douglas Daniels, James Petersson, and Jade Qiu, are all at Yale University. A story in the February 5, 2007, issue of Chemical & Engineering News spotlighted the research.

Original Article

Cheap, safe drug kills most cancers

2007-02-05T13:28:00.001-05:00

IT SOUNDS almost too good to be true: a cheap and simple drug that kills almost all cancers by switching off their "immortality". The drug, dichloroacetate (DCA), has already been used for years to treat rare metabolic disorders and so is known to be relatively safe. It also has no patent, meaning it could be manufactured for a fraction of the cost of newly developed drugs.

Evangelos Michelakis of the University of Alberta in Edmonton, Canada, and his colleagues tested DCA on human cells cultured outside the body and found that it killed lung, breast and brain cancer cells, but not healthy cells. Tumours in rats deliberately infected with human cancer also shrank drastically when they were fed DCA-laced water for several weeks.

DCA attacks a unique feature of cancer cells: the fact that they make their energy throughout the main body of the cell, rather than in distinct organelles called mitochondria. This process, called glycolysis, is inefficient and uses up vast amounts of sugar. Until now it had been assumed that cancer cells used glycolysis because their mitochondria were irreparably damaged. However, Michelakis's experiments prove this is not the case, because DCA reawakened the mitochondria in cancer cells. The cells then withered and died (Cancer Cell, DOI: 10.1016/j.ccr.2006.10.020).

Michelakis suggests that the switch to glycolysis as an energy source occurs when cells in the middle of an abnormal but benign lump don't get enough oxygen for their mitochondria to work properly (see Diagram). In order to survive, they switch off their mitochondria and start producing energy through glycolysis.

Crucially, though, mitochondria do another job in cells: they activate apoptosis, the process by which abnormal cells self-destruct. When cells switch mitochondria off, they become "immortal", outliving other cells in the tumour and so becoming dominant. Once reawakened by DCA, mitochondria reactivate apoptosis and order the abnormal cells to die.

"The results are intriguing because they point to a critical role that mitochondria play: they impart a unique trait to cancer cells that can be exploited for cancer therapy," says Dario Altieri, director of the University of Massachusetts Cancer Center in Worcester.

The phenomenon might also explain how secondary cancers form. Glycolysis generates lactic acid, which can break down the collagen matrix holding cells together. This means abnormal cells can be released and float to other parts of the body, where they seed new tumours.

DCA can cause pain, numbness and gait disturbances in some patients, but this may be a price worth paying if it turns out to be effective against all cancers. The next step is to run clinical trials of DCA in people with cancer. These may have to be funded by charities, universities and governments: pharmaceutical companies are unlikely to pay because they can't make money on unpatented medicines. The pay-off is that if DCA does work, it will be easy to manufacture and dirt cheap.

Paul Clarke, a cancer cell biologist at the University of Dundee in the UK, says the findings challenge the current assumption that mutations, not metabolism, spark off cancers. "The question is: which comes first?" he says.
From issue 2587 of New Scientist magazine, 20 January 2007, page 13

Original Article

Eating According to Your Genome

2007-01-31T13:31:00.001-05:00

The emerging field of nutrigenomics is starting to yield some DNA-based diet tips, says nutrition scientist Jose Ordovas.
By Emily Singer

If you knew that you were especially susceptible to heart disease when you gained weight, would it increase your motivation to diet? How much would you be willing to pay to find out if you are one of the lucky people who can eat as much fat as you want and not have an increased risk of heart disease? Such tests are the goal of nutrigenomics, which seeks to identify the links between nutrition and disease based on an individual's genome.

While the field is still too young to offer personal dietary advice for the average consumer, research has uncovered links among genes, diet, and heart disease. Jose Ordovas, director of the Nutrition and Genomics Laboratory at Tufts University, has spent years studying the link between metabolism of dietary fats and risk of cardiovascular disease. After analyzing data from the Framingham Heart Study, a large-scale study that has traced the health of some 5,000 people since 1948, his team has found that certain genetic variants can protect people from diet-induced cardiovascular disease--or put them at increased risk. Ordovas spoke with Technology Review about his research and the future of the field.

TR: Why is nutrigenomics important?

JO: Everybody knows that some people can smoke and live a long life or eat little and still gain weight. But we don't know in advance who these people are. If we did know, these people could be educated to try to avoid the health concerns that could hit later in life. [Nutrigenomics] offers the potential to understand the relationship between food and our health on an individual level.

TR: You have found a striking link between genetic variations in a gene known as apolipoprotein E, or APOE, and risk factors for heart disease, but only under certain dietary conditions.

JO: People with a certain variation, known as APOE e4, are born with a predisposition to heart disease. For these people, a high-fat diet, smoking, or a high BMI [body-mass index] is very bad. For example, they have higher blood glucose levels, a risk factor for heart disease, but only if they have a body-mass index over 30, which is considered obese.

But these people also respond much better to a low-fat, low-cholesterol diet. So they are the ones who should really follow dietary guidelines. If you want to select people for behavior modification, these are the people to start with.

TR: Can people get tested for their APOE variant?

JO: That's a tricky situation. If you have the APOE e4 variant, you're at increased risk for heart disease, which you can do something about. But you also have a higher risk for dementia, which we don't know if you can do anything about. So there are legal and ethical issues associated with testing.

TR: One of the current nutrition debates is over the benefits of omega-3 fatty acids--different studies have produced conflicting results regarding omega-3's ability to protect against heart disease. Can nutrigenomics help sort this out?

JO: We have found that some people are more susceptible to the negative effects of omega-6 [a related fatty acid] than others. Those with a certain variant in the apolipoprotein A, or APOA, gene show a rise in triglycerides, a risk factor for cardiovascular disease, when they eat a diet high in omega-6. In these cases, the protective effect of omega-3 may be overwhelmed by overconsumption of omega-6.

This allele is much more common in Asia, and those who have it are more susceptible to the effect of omega-6 consumption. That may explain the rising rates of cardiovascular disease in Asian populations.

TR: What are the major hurdles in identifying how our genes affect our body's response to food?

JO: There are so many combinations of genes and environmental factors, you need huge populations to study. Most studies in the field are underpowered. We've done studies with 5,000 people, but that's just not enough. We need to do studies on the order of 100,000 people to take into account all the different factors.

We also need better statistical tools. Currently, we are borrowing analysis tools from situations that are much simpler, such as Medelian genetics, where a single gene leads to a certain phenotype. But applying those methods to huge networks of interactions is just not feasible.

TR: Is the nutrigenomics community using new genetic tools, such as the large gene chips that can detect 500,000 genetic variations in a single experiment?

JO: Yes, those chips do help to accumulate data. But because we need to run thousands of subjects, the cost is still prohibitive.

TR: A few consumer nutrigenomics tests are already on the market. What do you think of them?

JO: These tests may point people in the right direction, but they are not by far a final answer. Their worth also depends on the feedback the consumer gets. If the test is accompanied by prudent recommendations on diet and does not make snake-oil promises, then they probably don't have much potential to harm. And they may even have some benefit. One study found that people who took the test and went to a dietician did better than people who just went to a dietician. I think it's the placebo effect. People will pay better attention because they feel they are getting advice that is just for them.

Copyright Technology Review 2007.

Original Article

Diabetes breakthrough

2007-01-09T10:10:00.001-05:00

Toronto scientists cure disease in mice

Tom Blackwell
National Post
Friday, December 15, 2006

In a discovery that has stunned even those behind it, scientists at a Toronto hospital say they have proof the body's nervous system helps trigger diabetes, opening the door to a potential near-cure of the disease that affects millions of Canadians.

Diabetic mice became healthy virtually overnight after researchers injected a substance to counteract the effect of malfunctioning pain neurons in the pancreas.

"I couldn't believe it," said Dr. Michael Salter, a pain expert at the Hospital for Sick Children and one of the scientists. "Mice with diabetes suddenly didn't have diabetes any more."

The researchers caution they have yet to confirm their findings in people, but say they expect results from human studies within a year or so. Any treatment that may emerge to help at least some patients would likely be years away from hitting the market.

But the excitement of the team from Sick Kids, whose work is being published today in the journal Cell, is almost palpable.

"I've never seen anything like it," said Dr. Hans Michael Dosch, an immunologist at the hospital and a leader of the studies. "In my career, this is unique."

Their conclusions upset conventional wisdom that Type 1 diabetes, the most serious form of the illness that typically first appears in childhood, was solely caused by auto-immune responses -- the body's immune system turning on itself.

They also conclude that there are far more similarities than previously thought between Type 1 and Type 2 diabetes, and that nerves likely play a role in other chronic inflammatory conditions, such as asthma and Crohn's disease.

The "paradigm-changing" study opens "a novel, exciting door to address one of the diseases with large societal impact," said Dr. Christian Stohler, a leading U.S. pain specialist and dean of dentistry at the University of Maryland, who has reviewed the work.

"The treatment and diagnosis of neuropathic diseases is poised to take a dramatic leap forward because of the impressive research."

About two million Canadians suffer from diabetes, 10% of them with Type 1, contributing to 41,000 deaths a year.

Insulin replacement therapy is the only treatment of Type 1, and cannot prevent many of the side effects, from heart attacks to kidney failure.

In Type 1 diabetes, the pancreas does not produce enough insulin to shift glucose into the cells that need it. In Type 2 diabetes, the insulin that is produced is not used effectively -- something called insulin resistance -- also resulting in poor absorption of glucose.

The problems stem partly from inflammation -- and eventual death -- of insulin-producing islet cells in the pancreas.

Dr. Dosch had concluded in a 1999 paper that there were surprising similarities between diabetes and multiple sclerosis, a central nervous system disease. His interest was also piqued by the presence around the insulin-producing islets of an "enormous" number of nerves, pain neurons primarily used to signal the brain that tissue has been damaged.

Suspecting a link between the nerves and diabetes, he and Dr. Salter used an old experimental trick -- injecting capsaicin, the active ingredient in hot chili peppers, to kill the pancreatic sensory nerves in mice that had an equivalent of Type 1 diabetes.

"Then we had the biggest shock of our lives," Dr. Dosch said. Almost immediately, the islets began producing insulin normally "It was a shock ? really out of left field, because nothing in the literature was saying anything about this."

It turns out the nerves secrete neuropeptides that are instrumental in the proper functioning of the islets. Further study by the team, which also involved the University of Calgary and the Jackson Laboratory in Maine, found that the nerves in diabetic mice were releasing too little of the neuropeptides, resulting in a "vicious cycle" of stress on the islets.

So next they injected the neuropeptide "substance P" in the pancreases of diabetic mice, a demanding task given the tiny size of the rodent organs. The results were dramatic.

The islet inflammation cleared up and the diabetes was gone. Some have remained in that state for as long as four months, with just one injection.

They also discovered that their treatments curbed the insulin resistance that is the hallmark of Type 2 diabetes, and that insulin resistance is a major factor in Type 1 diabetes, suggesting the two illnesses are quite similar.

While pain scientists have been receptive to the research, immunologists have voiced skepticism at the idea of the nervous system playing such a major role in the disease. Editors of Cell put the Toronto researchers through vigorous review to prove the validity of their conclusions, though an editorial in the publication gives a positive review of the work.

"It will no doubt cause a great deal of consternation," said Dr. Salter about his paper.

The researchers are now setting out to confirm that the connection between sensory nerves and diabetes holds true in humans. If it does, they will see if their treatments have the same effects on people as they did on mice.

Nothing is for sure, but "there is a great deal of promise," Dr. Salter said.

© National Post 2006

Cancer-Killing Invention Also Harvests Stem Cells

2007-01-08T15:15:00.000-05:00

by Lois H. Gresh

Associate Professor Michael King of the University of Rochester Biomedical Engineering Department has invented a device that filters the blood for cancer and stem cells. When he captures cancer cells, he kills them. When he captures stem cells, he harvests them for later use in tissue engineering, bone marrow transplants, and other applications that treat human disease and improve health. With Nichola Charles, Jared Kanofsky, and Jane L. Liesveld of the University of Rochester, King wrote about his discoveries in "Using Protein-Functionalized Microchannels for Stem Cell Separation," Paper No. ICNMM2006-96228, Proceedings of the ASME, June 2006. King’s team includes scientists at StemCapture, Inc., a Rochester company that bought the University patent for King’s technique in November 2005 to build the cancer-killing and stem cell-harvesting devices. The technique can be used in vivo, meaning a device is inserted in the body, or in vitro, in which case the device resides outside of the body – either way, the device kills cancer cells and captures stem cells, which grow into blood cells, bone, cartilage, and fat.

When King was working at the University of Pennsylvania from 1999 to 2001, one of his labmates discovered that bone marrow stem cells stick to adhesive proteins called selectins more strongly than other cells -- including blood cells -- stick to selectins. When King came to the University of Rochester in early 2002, he started studying the adhesion of blood cells to the vascular wall, the inner lining of the blood vessels. During inflammation, the vascular wall presents surface selectins that adhere specifically to white blood cells. These selectins cause the white blood cells to roll slowly along the vascular wall, seeking signals that tell them to crawl out of the bloodstream. This is how white blood cells migrate to bacterial infections and tissue injuries. King set out to find a way to duplicate this natural process.

First, he noted that the selectins form bonds with the white blood cells within fractions of a second, then immediately release the cells back into the bloodstream. He also realized that selectin is the adhesive mechanism by which bone marrow stem cells leave the bloodstream and find their way back into bone marrow. This is how bone marrow transplantation works. Finally, he learned that when a cancer cell breaks free of a primary tumor and enters circulation, it flow through the bloodstream to a remote organ, then leaves the bloodstream and forms a secondary tumor. This is how cancer spreads. He put these facts together with one more, very important fact: the selectins grab onto a specific carbohydrate on the surfaces of white blood cells, stem cells, and cancer cells. Associate Professor King decided to capture stem and cancer cells before the selectins release them.

Harvesting Stem Cells

Because bone marrow stem cells stick to selectin surfaces more strongly than other cells, King’s group coated a slender plastic tube with selectin. They then did a series of lab experiments, both in vitro and in vivo using rats, with this selectin-coated tube to filter the bloodstream for stem cells. It worked, and the King Lab discovered that they could attract a large number of cells to the wall of their selectin-coated device, and that 38% of these captured cells were stem cells. King envisioned a system by which doctors could remove stem cells from the bloodstream by flowing the cells through a device, and make a more concentrated mixture containing, say, 20-40 percent stem cells. These stem cells could then be used for tissue engineering or bone marrow transplantation.

This is a non-controversial way of obtaining stem cells that can be differentiated into other, useful cells.

Michael King's Device Supplies a Concentrated Mixure of Stem Cells:

King’s team can capture significant amounts of cells of the lymphatic and circulatory systems, and potentially mesenchymal stem cells, which are unspecialized cells that form tissue, bone, and cartilage. Current procedures enable the specific capture of hematopoietic stem cells, which grow (or differentiate) over time into all of the different blood cells, and the specific capture of stem cells that differentiate into bone marrow cells. The device itself uses a combination of microfluidics, or fluid flow properties, and specialized selectin coatings.

Killing Cancer Cells:

Another exciting application of King’s invention is filtering the blood for cancer cells and triggering their death, an innovative, new method to prevent the spread of cancer. When someone has a primary cancer tumor, a small number of cancer cells circulates through the bloodstream. In a process called metastasis, these cells are transmitted from the primary tumor to other locations in the body, where they form secondary, cancerous growths.

As a cancer cell flows along the implanted surface, King’s device captures it and delivers an apoptosis signal, a biochemical way of telling the cancer cell to kill itself. Within two days, that cancer cell is dead. Normal cells are left totally unharmed because the device selectively targets cancer cells.

The apoptosis signal is delivered by a molecule called TRAIL that coats the cancer-killing device. Cancer cells have five types of proteins that recognize and bind to TRAIL, but only two trigger cell death. The other three are called decoy receptors. Healthy cells contain a lot of decoy receptors, giving them a natural protection against TRAIL, whereas cancer cells mainly express the two receptors that signal cell death.

Michael King's Device Kills Cancer Cells:

During the death of the cancer cells, TRAIL is not depleted or used up in any way, and in fact, it stays active for many weeks or months. The same TRAIL molecules can kill enormous numbers of cancer cells.

A possible way to use the cancer-killing invention is to implant the device in the body before primary tumor surgery or chemotherapy. When doctors remove a primary tumor, the procedure itself can release cancer cells into the bloodstream. King’s device would grab those cancer cells and kill them, greatly reducing the possibility of metastasis.

Associate Professor King envisions that the device would use a shunt similar to the type used in hospitals today. This shunt would reside on the exterior of the arm or be implanted beneath the skin. Some of the blood flow would bypass the capillary bed and instead go into the shunt, which could remain implanted for many weeks, continually removing and killing cancer cells. King’s first targets are colorectal cancer and blood malignancies such as leukemia.

Growing New Limbs the Zebrafish Way

2006-12-29T16:57:00.001-05:00

A zebrafish tail fin one day after amputation is shown on the left. The image on the right shows that by ten days post amputation, the tail fin has regenerated.

A lost tail fin can really slow down a zebrafish - at least for a week or so, until it grows a new one. Now scientists have shown that they can turn on or block this regeneration in zebrafish with the flip of a molecular switch. Understanding how the fish's cells coordinate the regrowth of the structurally complex fin can help scientists understand the process of regeneration, providing clues that may aid in the development of new clinical therapies, such as renewing cardiac tissue after heart disease.

The scientists said that not only will their findings advance research aimed at regenerating tissues and organs, but the discoveries could also lead to improved therapies for bone marrow transplants to restore the hematopoetic system in cancer patients.

"In studying injury or inflammation in any context, investigators should explore whether Wnt signaling is involved. These experiments suggest that Wnt signaling is a universal component of regenerative pathways in animals."
Randall T. Moon

The researchers' findings were published online December 22, 2006, as a Development ePress article, which is posted in advance of print publication in the journal Development. The senior author was Howard Hughes Medical Institute investigator Randall Moon at the Institute for Stem Cell and Regenerative Medicine of the University of Washington School of Medicine, and the joint first authors were Cristi Stoick-Cooper and Gilbert Weidinger, who designed and carried out the experiments in the Moon laboratory.

Using tail fin regeneration in the zebrafish as a model system, the researchers discovered that a major cellular signaling pathway, called the Wnt/ß-catenin pathway, is central to activating the complex machinery of limb regeneration. This pathway is known to play a major role in regulating stem cells in embryonic development and adult tissue maintenance. Malfunctions in the pathway have been proven to lead to cancers, as well as being linked to bone density diseases and neurodegenerative diseases.

The Wnt/ß-catenin pathway comprises a large group of proteins that are activated when the signaling molecule Wnt binds to the pathway's cell surface receptors. This activation increases the levels of ß-catenin - a master regulator of multiple genes - that reach the cell nucleus.

The researchers also found that a related Wnt protein, called wnt5b, inhibited regeneration. Wntb5 governs a signaling pathway that is independent of ß-catenin. So, Wnt proteins can turn on more than one signaling pathway, and both are involved in regeneration, though with opposite roles.

"It was previously known that Wnt pathway components were expressed during regeneration, but nobody had really explored whether the pathways were indeed activated," said Moon. "And nobody had separated the two pathways and looked at their effects individually."

In their experiments, Stoick-Cooper and Weidinger genetically manipulated the Wnt/ß-catenin pathway in the fish and measured how that manipulation affected the fish's ability to regrow an amputated tail fin.

Using a fluorescent "reporter" gene that revealed Wnt/ß-catenin pathway activation by glowing like a firefly, the scientists showed that the pathway was clearly switched on during regeneration, just in the area of the body that was regenerating. Similarly, they saw that the pathway was activated during regeneration of zebrafish heart and mouse liver, which they said suggests that the pathway may function in regeneration across species. They further noted that the Wnt/ß-catenin pathway was activated during the formation of the undifferentiated cells that proliferate to regenerate the tail fin.

They next genetically engineered fish in which they could switch off the Wnt/ß-catenin pathway by exposing the fish to warm water. Doing so, they found, completely blocked regeneration. They could also accelerate regeneration by enhancing Wnt/ß-catenin signaling. The researchers noted that this is a significant finding for the new field of regenerative medicine, in which a means of enhancing regeneration is an invaluable tool.

In contrast, when they engineered fish to activate the wnt5b gene in response to warm water, regeneration was inhibited. The opposite is true in fish with a mutation in the wnt5b gene, in which they found that regeneration was augmented. This is what one would expect, Moon noted, since the loss of a functional inhibitor is a double negative meaning that regeneration should be accelerated.

"These experiments showed that there is a completely novel and unexpected mechanism that antagonizes the regenerative process," said Moon. "There had been other studies indicating that wnt5b-like genes could block the Wnt/ß-catenin pathway, but no one had examined whether this antagonism occurs in the context of the normal regenerative process."

"Cristi and Gilbert's experiments rigorously establish through genetic approaches that the Wnt pathways are functionally important in regeneration," he said. "More generally, they show that in studying injury or inflammation in any context, investigators should explore whether Wnt signaling is involved. These experiments suggest that Wnt signaling is a universal component of regenerative pathways in animals," he said.

According to Moon, the findings by Stoick-Cooper and Weidinger will have clinical implications for tissue regeneration, as well as for encouraging growth of stem cells. Stem cells are immature, undifferentiated cells that are capable of maturing into a variety of mature cell types.

"Wnt/ß-catenin signaling plays an important positive role in the differentiation of stem cells and progenitor cells that are required for regeneration," he said. "It agrees with previous studies in which our laboratory showed in animals that activating this pathway increases the success of transplants of blood-forming hematopoietic stem cells. Such transplants in cancer patients whose immune systems have been destroyed by radiation or chemotherapy are invaluable as therapy; and sometimes they fail because they transplanted cells do not engraft into the bone marrow. We believe that enhancing the Wnt/ß-catenin pathway will increase the success rate of such hematopoietic stem cell transplants," he said.

In other clinically-related studies, Moon and his colleagues are exploring whether activating the Wnt/ß-catenin pathway can enhance differentiation of human embryonic stem cells into cardiac cells that could be used to treat heart disease

Moon and his colleagues are also exploring how the myriad different kinds of cells involved in regeneration respond to Wnt-activating signals and, in collaboration with HHMI investigator Leonard I. Zon at Children's Hospital, Boston, how injury switches on Wnt/ß-catenin signaling. The researchers are optimistic that Wnt signaling will be an important therapeutic target in the growing field of regenerative medicine.

Original Article

Insuling, aging, and mass

2006-12-15T13:49:00.001-05:00

Scientists from the new interdisciplinary LIMES (Life & Medical Sciences) Centre at the University of Bonn have identified a new gene which could play an important role in the development of diabetes. Flies in which this hereditary factor is defective are also significantly smaller than other members of their species and live appreciably longer. The gene seems to have such a crucial function that it has hardly changed in just under a billion years: it is found in flies, but in a similar form it is also found in mice and humans. In the current issue of the prestigious journal Nature the Bonn researchers have published two articles on this topic.

Sometimes science resembles a relay race: in 1996 the biochemist Professor Waldemar Kolanus discovered a group of cellular proteins, the cytohesins, and described their function in the immune system. Two of his colleagues at the LIMES Centre in Bonn have now found a totally new and completely unexpected function of these proteins which is very relevant to medicine. 'We wanted to know whether there were also cytohesins in the fruit fly drosophila and what functions they have there,' the evolutionary biologist Professor Michael Hoch reminisces. He and his team were in fact successful. They discovered a protein which is very similar to the cytohesins in mammals. Even more interestingly, fruit flies in which the genetic blueprint for this gene is defective are smaller in size. So the researchers nicknamed cytohesin 'Titch'. 'The effect on the insect's growth showed us that 'Titch' could play a key role in the metabolism of insulin – a completely new role for cytohesins,' Professor Hoch says.

New anti-aging ingredient

2006-12-15T13:37:00.000-05:00

A new anti-aging ingredient developed by UNSW researchers is expected to be available in skin products as early as next year.

Known as GGC, it is a precursor for an effective antioxidant known as glutathione, that has a broad range of potential health benefits. Glutathione is the body's key defence for detoxifying harmful compounds implicated in cancer, diabetes, aging and other diseases and degenerative conditions.

After nine years in development, UNSW researchers Dr Wallace Bridge and Dr Martin Zarka have established a new, cost-effective process for manufacturing GGC, which has been licensed to pharmaceutical company, Biospecialties Australia. A newly-expanded manufacturing plant at Mayfield, near Newcastle, will produce GGC.

It is expected that GGC will be used as an active ingredient in foods, health care, toothpastes, dietary supplements and cosmetics as well as in skin repair anti-aging creams.

Original Article

New Observations On Properties Of Water

2006-12-14T08:38:00.001-05:00

Recent research on the properties of water reveals information relevant for cloud physics and even cryopreservation science.

Experimental studies conducted by Ph.D. Anatoli Bogdan at the University of Helsinki, Finland, have received broad interest in the scientific world, as the results might have applications even in the cryopreservation of cells and tissues. Bogdan's results show that mixture droplets consisting of sulphuric acid and water can be slowly cooled down to-140 degrees Celsius and then heated again without ice formation. The formation of ice is particularly problematic in cryopreservation, as the crystal formation damages cell structures.

Bogdan has conducted his experiments by cooling and heating droplets of 0.5-6 µm in diameter. His study focuses on two forms of water: low-density amorphous ice (LDA, or so-called glassy water) and highly viscous water (HVW), which is a liquid phase that LDA melts into. Bogdan reports that HVW is not a new form of water as some scientists believed. Bogdan's study Reversible Formation of Glassy Water in Slowly cooling Diluted Drops has been published in Journal of Physical Chemistry in June 2006.

Bogdan himself applies his observations on the properties of water in cloud research, and he and his colleagues have recently published a study dealing with cirrus clouds (Formation of Low-Temperature Cirrus from H2SO4/H2O Aerosol Droplets, Journal of Physical Chemistry, November 2006). Their study suggests that, unlike previously thought, the cloud crystals in cirrus clouds are not completely solid ice, but are covered with a layer of liquid water and sulphuric acid. The layer effects for instance the reflectivity of the clouds, and therefore the climate. It has also been observed that the rate of ozone loss is higher on liquid than on solid surfaces. The results therefore indicate that the ozone is destroyed in the cirrus clouds faster than conventionally has been thought.

Original Article

Forsyth Scientists Discover Early Key to Regeneration

2006-12-13T11:26:00.000-05:00

Science may be one step closer to understanding how a limb can be grown or a spinal cord can be repaired. Scientists at The Forsyth Institute have discovered that some cells have to die for regeneration to occur. This research may provide insight into mechanisms necessary for therapeutic regeneration in humans, potentially addressing tissues that are lost, damaged or non- functional as a result of genetic syndromes, birth defects, cancer, degenerative diseases, accidents, aging and organ failure. Through studies of the frog (Xenopus) tadpole, the Forsyth team examined the cellular underpinnings of regeneration.

The Xenopus tadpole is an ideal model for studying regeneration because it is able to re-grow a fully functioning tail and all of its components, including muscle, vasculature, skin, and spinal cord. The Forsyth scientists studied the role that apoptosis, a process of programmed cell death in multi-cellular organisms, plays in regeneration. The research team, led by Michael Levin, Ph.D., Director of the Forsyth Center for Regenerative and Developmental Biology, found that apoptosis has a novel role in development and a critical role in regeneration. According to Dr. Levin, “Simply put, some cells have to die for regeneration to happen.”

The findings will be published in the January 1, 2007 issue of Developmental Biology (v301i1). “We were surprised to see that some cells need to be removed for regeneration to proceed,” said Ai-Sun Tseng, Ph.D. the paper’s first author. “It is exciting to think that someday this process could be managed to allow medically therapeutic regeneration.”

Summary of Study

In the context of efforts to understand biophysical controls of regenerative processes, The Forsyth Center for Regenerative and Developmental Biology investigated the dynamics of cell number control in the regenerating tail bud. Previous research in the field has shown that one mechanism by which cell number is controlled is by programmed cell death, which has been shown to be involved in sculpting of growing tissue in a number of developmental systems including heart, limb and craniofacial patterning. This study shows that despite the massive tissue proliferation required to build the tail, an early apoptotic event is required for regeneration. Normal regeneration of the tail includes a small focus of apoptotic cells; when apoptosis is inhibited during the first 24 hours, regeneration cannot proceed and the growth of nerve axons becomes abnormal. Later inhibition of apoptosis has no effect, suggesting that the programmed death of a specific cellular component is a very early step in the regeneration program. One possible model is that tissues normally contain a population of cells whose purpose is to prevent massive growth in the region surrounding them. Future work by the Levin group will identify the cells that must die, in order to try to understand the signals that cells utilize for growth control.

Michael Levin, PhD. is an Associate Member of the Staff in The Forsyth Institute Department of Cytokine Biology and the Director of the Forsyth Center for Regenerative and Developmental Biology. Through experimental approaches and mathematical modeling, Dr. Levin and his team examine the processes governing large-scale pattern formation and biological information storage during animal embryogenesis. The lab’s investigations are directed toward understanding the mechanisms of signaling between cells and tissues that allows a living system to reliably generate and maintain a complex morphology. The Levin team studies these processes in the context of embryonic development and regeneration, with a particular focus on the biophysics of cell behavior.

The Forsyth Institute is the world’s leading independent organization dedicated to scientific research and education in oral, craniofacial and related biomedical sciences.

Original Article

Growing heart muscle

2006-12-11T09:46:00.001-05:00

ANN ARBOR, Mich. — It looks, contracts and responds almost like natural heart muscle – even though it was grown in the lab. And it brings scientists another step closer to the goal of creating replacement parts for damaged human hearts, or eventually growing an entirely new heart from just a spoonful of loose heart cells.

This week, University of Michigan researchers are reporting significant progress in growing bioengineered heart muscle, or BEHM, with organized cells, capable of generating pulsating forces and reacting to stimulation more like real muscle than ever before.

The three-dimensional tissue was grown using an innovative technique that is faster than others that have been tried in recent years, but still yields tissue with significantly better properties. The approach uses a fibrin gel to support rat cardiac cells temporarily, before the fibrin breaks down as the cells organize into tissue.

The U-M team details its achievement in a new paper published online in the Journal of Biomedical Materials Research Part A.

And while BEHM is still years away from use as a human heart treatment, or as a testing ground for new cardiovascular drugs, the U-M researchers say their results should help accelerate progress toward those goals. U-M is applying for patent protection on the development and is actively looking for a corporate partner to help bring the technology to market.

Ravi K. Birla, Ph.D., of the Artificial Heart Laboratory in U-M's Section of Cardiac Surgery and the U-M Cardiovascular Center, led the research team.

"Many different approaches to growing heart muscle tissue from cells are being tried around the world, and we're pursuing several avenues in our laboratory," says Birla. "But from these results we can say that utilizing a fibrin hydrogel yields a product that is ready within a few days, that spontaneously organizes and begins to contract with a significant and measurable force, and that responds appropriately to external factors such as calcium."

The new paper actually compares two different ways of using fibrin gel as a basis for creating BEHM: layering on top of the gel, and embedding within it. In the end, the layering approach produced a more cohesive tissue that contracted with more force – a key finding because embedding has been seen as the more promising technique.

The ability to measure the forces generated by the BEHM as it contracts is crucial, Birla explains. It's made possible by a precise instrument called an optical force transducer that gives more precise readings than that used by other teams.

The measurement showed that the BEHM that had formed in just four days after a million cells were layered on fibrin gel could contract with an active force of more than 800 micro-Newtons. That's still only about half the force generated within the tissue of an actual beating heart, but it's much higher than the forces created by engineered heart tissue samples grown and reported by other researchers. Birla says the team expects to see greater forces created by BEHM in future experiments that will bathe the cells in an environment that's even more similar to the body's internal conditions.

In the new paper, the team reports that contraction forces increased when the BEHM tissues were bathed in a solution that included additional calcium and a drug that acts on beta-adrenergic receptors. Both are important to the signaling required to produce cohesive action by cells in tissue.

The U-M team also assessed the BEHM's structure and function at different stages in its development. First author and postdoctoral fellow Yen-Chih Huang, Ph.D., of the U-M Division of Biomedical Engineering, led the creation of the modeling system. Co-author and research associate Luda Khait examined the tissue using special stains that revealed the presence and concentration of the fibrin gel, and of collagen generated by the cells as they organized into tissue.

Over the course of several days, the fibrin broke down as intended, after fulfilling its role as a temporary support for the cells. This may be a key achievement for future use of BEHM as a treatment option, because the tissue could be grown and implanted relatively quickly.

The U-M Artificial Heart Laboratory (www.sitemaker.umich.edu/ahl) is part of the U-M Section of Cardiac Surgery, and draws its strength from the fact that it includes bioengineers, cell biologists and heart surgeons – a multidisciplinary group that can tackle both the technical and clinical hurdles in the field of engineering heart muscle. Its focus is to evaluate different platforms for engineering cardiovascular structures in the laboratory. Active programs include tissue engineering models for cardiac muscle, tri-leaflet valves, cell-based cardiac pumps and vascular grafts. In addition, the laboratory has expertise in several different tissue engineering platforms: self-organization strategies, biodegradable hydrogels such as fibrin, and polymeric scaffolds.

Each approach may turn out to have its own applications, says Birla, and the ability to conduct side-by-side comparisons is important. Other researchers have focused on one approach or another, but the U-M team can use its lab to test multiple approaches at once.

"Fundamentally, we're interested in creating models of the different components of the heart one by one," says Birla.

"It's like building a house – you need to build the separate pieces first. And once we understand how these models can be built in the lab, then we can work toward building a bioengineered heart." He notes that while many other labs focus on growing one heart component, only U-M is working on growing all the different heart components.

Already, the U-M team has begun experiments to transplant BEHM into the hearts of rats that have suffered heart attacks, and see if the new tissue can heal the damage. This work is being conducted by Francesco Migneco, M.D., a research fellow with the Artificial Heart Laboratory. Further studies will implement "bioreactors" that will expose the BEHM tissue to more of the nutrients and other conditions that are present in the body.

evolutionary risk of cancer based on body mass

2006-12-06T09:44:00.000-05:00

A key enzyme that cuts short our cellular lifespan in an effort to thwart cancer has now been linked to body mass.

Until now, scientists believed that our relatively long lifespans controlled the expression of telomerase--an enzyme that can lengthen the lives of cells, but can also increase the rate of cancer.

Vera Gorbunova, assistant professor of biology at the University of Rochester, conducted a first-of-its-kind study to discover why some animals express telomerase while others, like humans, don't. The findings are reported in today's issue of Aging Cell.

"Mice express telomerase in all their cells, which helps them heal dramatically fast," says Gorbunova. "Skin lesions heal much faster in mice, and after surgery a mouse's recovery time is far shorter than a human's. It would be nice to have that healing power, but the flip side of it is runaway cell reproduction--cancer."

Up until now, scientists assumed that mice could afford to express telomerase, and thereby benefit from its curative powers, because their natural risk of developing cancer is low--they simply die before there's much likelihood of one of their cells becoming cancerous.

"Most people don't know that if you put mice in a cage so the cat can't eat them, 90 percent of them will die of cancer," says Gorbunova.

Evolution, it seems, has determined which species are allowed to express telomerase in their somatic cells in order to maintain a delicate balance between cells that live long, and cells that become cancerous. But while most scientists believed an organism's lifespan determined whether it was at a higher risk of cancer, Gorbunova has revealed evidence that it is not our long lifespan that puts us at risk, but our much-heavier-than-a-mouse body mass.

The tips of chromosomes, called telomeres, shorten every time a cell divides. After about 60 divisions, the telomeres are eroded away to the point that the cell stops dividing. Telomerase rebuilds those tips, so animals that express it, like mice, have cells that can reproduce more extensively and thus heal better. Cancer cells, however, are those cells that constantly reproduce unchecked, and so evolution has shut off the expression of telomerase in human somatic cells, presumably because the threat of cancer outweighs the benefits of quick-healing.

But no one has looked into why mice express telomerase and humans don't. In fact, telomerase activity has been barely catalogued in the animal kingdom. Gorbunova decided to take on the question by creating a unique test. She investigated 15 rodents from across the globe to determine what level of telomerase activity each species expressed, to see if there were some correlation she could find.

The species ranged from tiny field mice to the 100-pound capybara from Brazil. Lifespans ranged from three years for the mice, to 23 or more for common backyard squirrels.

Acquiring specimens of these animals from around the world proved to be an unusual task.

"At one point I was woken up at two in the morning by a guy on a cell phone hunting pest beavers in Montezuma," says Gorbunova. "I'm still trying to wake up and this voice says, 'I hear you're looking for beavers.' "

For over a year, Gorbunova collected deceased rodents from around the world and had them shipped to her lab in chilled containers. She analyzed their tissues to determine if the telomerase was fully active in them, as it was in mice, or suppressed, as it is in humans. Rodents are close to each other on the evolutionary tree and so if there were a pattern to the telomerase expression, she should be able to spot it there.

To her surprise, she found no correlation between telomerase and longevity. The great monkey wrench in that theory was the common gray squirrel, which lives an amazing two decades, yet also expresses telomerase in great quantity. Evolution clearly didn't see long life in a squirrel to be an increased risk for cancer. Body mass, however, showed a clear correlation across the 15 species. The capybara, nearly the size of a grown human, was not expressing telomerase, suggesting evolution was willing to forgo the benefits in order to reign in cancer.

The results cannot be directly related to humans, but Gorbunova set up the study to produce very strong across-the-board indicators. It's clear that evolution has found that the length of time an organism is alive has little effect on how likely some of its cells might mutate into cancer. Instead, simply having more cells in your body does raise the specter of cancer--and does so enough that the benefits of telomerase expression, such as fast healing, weren't worth the cancer risk.

Gorbunova points out that these findings raise another, perhaps far more important question: What, then, does this mean for animals that are far larger than humans? If a 160-pound human must give up telomerase to thwart cancer, then what does a 250,000-pound whale have to do to keep its risk of cancer at bay? "It may be that whales have a cancer suppressant that we've never considered," says Gorbunova. "I'd like to find out what kind of telomerase expression they have, and find out what else they use to combat cancer."

Original Article

Deciphering Drosophila DNA

2006-12-04T12:14:00.000-05:00

P(acman) -- a new method of introducing DNA into the genome of fruit
flies or Drosophila -- promises to transform the ability of scientists
to study the structure and function of virtually all the fly's genes,
and the method may be applicable to other frequently studied organisms
such as mice, said its Baylor College of Medicine developers in an
article in the current issue of the journal Science.

"P(acman) overcomes a key limitation of currently available methods
because it allows you to study large chunks of DNA in vivo," said Dr.
Hugo Bellen, professor of molecular and human genetics at Baylor College
of Medicine and director of the program in developmental biology. He is
also a Howard Hughes Medical Institute investigator. The new technique
allows researchers to study large genes and even gene complexes in the
fruit fly, which was not possible before.

P/phiC31 artificial chromosome for manipulation, or P(acman), combines
three recently developed technologies: a specially designed bacterial
artificial chromosome (BAC) that allows maintenance of large pieces of
DNA in bacteria, recombineering that allows the manipulation of large
pieces of DNA that can then be inserted into the genome of the fly at a
specific site using phiC31-mediated transgenesis.

It is a new technique with far-reaching promise, said Bellen.

P(acman) overcomes certain obstacles that have hampered research. It
allows the cloning of large pieces of DNA to be used to transform the
genome, and it permits that DNA to be inserted into specific places in
the genome. Bellen credits the report's first author, Koen J.T. Venken,
a graduate student in the BCM Program in Developmental Biology, with
putting the technologies together to come up with a new methodology in
the field.

Current technology has certain problems for researchers seeking to
understand the structure and function of genes, said Bellen. Often, when
scientists breed flies that lack a particular gene and then try to put
that gene back into the fly, it inserts itself randomly into the genetic
blueprint.

In some cases, it makes too much protein, and in others, too little. In
other instances, it may disrupt the message from another gene.

"You are really comparing apples and oranges when you do this," said
Bellen. The technique is also limited to small DNA chunks.

"Koen set out to develop a new transgenesis system using the three
techniques," said Bellen.

The bacterial artificial chromosome, or BAC, he used allows the
scientist to maintain large chunks of DNA in the bacteria, but it is
present in only one or few copies. However, the bacteria can be induced
to produce many copies of the DNA when needed.

Koen then integrated a technique called "recombineering" into the
strategy, which facilitates the scientist to clone large chunks of DNA
and subsequently allows them to make specific mutations anywhere he or
she wants in the gene.

The third technique allows the researcher to pinpoint where he or she
wants to the mutant gene to go in the genetic blueprint of the fly,
eliminating the apples-and-oranges problem. This third technique --
phiC31 -- works also in mouse and human cells, implying that this new
technique could be used in those cells as well.

Others who contributed to this report include Yuchun He, also of BCM,
and Dr. Roger A. Hoskins of Lawrence Berkeley National Laboratory in
Berkeley, California.

The work was supported by the National Institutes of Health and the
Howard Hughes Medical Institute.

Original Article
<http://www.sciencedaily.com/releases/2006/11/061130191541.htm>

Mitochondrial oxidant generation is involved in determining why females live longer than males.

2006-12-01T12:32:00.000-05:00

Catholic University of Valencia, Spain.

Females live longer than males in many mammalian species, including humans. This natural phenomenon can be explained on the basis of the mitochondrial theory of aging. Mitochondria are a major source of free radicals in cells. Mitochondria from female rats generate half the amount of hydrogen peroxide than those of males and have higher levels of mitochondrial reduced glutathione. The latter is due to females behaving as double transgenic in over-expressing antioxidant enzymes. Estrogens bind to the estrogen receptors and subsequently activate the mitogen activated protein (MAP) kinase and nuclear factor kappa B (NFkappaB) signalling pathways, resulting in an upregulation of antioxidant enzymes. Moreover, the 16S rRNA expression, which decreases significantly with aging, is four times higher in mitochondria from females than in those from males of the same chronological age. On the contrary, the oxidative damage of mitochondrial DNA is fourfold higher in males than in females. Ovariectomy abolishes the gender differences between males and females and estrogen replacement rescues the effect of ovariectomy. The challenge for the future is to find molecules that have the beneficial effects of estradiol, but without its feminizing effects. Phytoestrogens or phytoestrogen-related molecules may be good candidates to meet this challenge.

Original Article

Link identified between age, cardiovascular disease

2006-11-26T00:46:00.000-05:00

CORVALLIS, Ore. -- Researchers in the Linus Pauling Institute at Oregon State University have discovered a fundamental mechanism that causes aging blood vessels to lose their elasticity – a literal "hardening of the arteries" that is often a prelude to high blood pressure and cardiovascular disease.

An understanding of this mechanism, scientists say, provides an important new target for both drugs and dietary changes that might help prevent or treat atherosclerosis and heart disease. This is a leading cause of death around the world that, in some form, affects about 80 percent of older Americans.

The findings were just published in Aging Cell, a professional journal. The study was funded by the National Institute on Aging, National Center for Complementary and Alternative Medicine, and the American Heart Association.

"This could ultimately provide a new, fundamental and possibly inexpensive way to treat or prevent high blood pressure," said Tory Hagen, an OSU associate professor of biochemistry and biophysics, and lead author on the study. "It's also a key to understanding the biological effects of inflammation, which increasingly seems to be implicated not only in heart disease but other chronic and neurologic diseases."

The research, which was done in test tubes and animal models, needs to be confirmed in humans before it could form the basis for new therapies. But the fundamental findings reveal an important insight into how blood vessels change with age and lose much of their ability to relax, contract, and facilitate the circulation of blood in the body.

Blood vessels in humans, like those of other animals, have vascular "smooth muscles" that can alternatively relax and contract to accommodate fluctuations in blood flow and volume. A thin layer of "endothelial cells" in the vessels serves, in part, as a sensor mechanism to help regulate this process. And proper function of the endothelial cells, in turn, is driven by specific enzymes and signaling pathways.

What has been known for some time is that blood vessels, as they age, lose much of their capacity to relax – according to the OSU research, about half of that capacity, even in healthy vessels. If the vessels are narrowed by atherosclerotic lesions the problem is further exacerbated. High blood pressure is often the result, which in turn can lead to heart attacks, strokes, and death.

Some of the most common high blood pressure medications, in fact, function by helping to address this loss of elasticity in blood vessels. The nitroglycerin pills used by many people with unstable angina provide an immediate boost of nitric oxide, which serves to relax blood vessels.

What has not been known is exactly why this "hardening" of the blood vessels occurs with age. The new OSU study answers much of that question. "Basically, we've learned that in older blood vessels, the cellular signaling process is breaking down," said Hagen. "The vessels still have the ability to relax much as they did when they were younger, but they are not getting the message."

A complex enzymatic process outlined in the new study explains how this "failure to communicate" occurs. An enzymatic reaction called "phosphorylation," which is essential to the signaling process, loses about half of its effectiveness in aging blood vessels. This loss of phosphorylation is due to less activity in one enzyme, AKT, that facilitates the process, and excess activity of phosphatases, that reverse it.

The researchers also discovered that ceramides, one type of lipid, or fat, are primarily responsible for the excessive activity of phosphatases. And in laboratory experiments with blood vessels from rats, they were able to inhibit ceramide synthesis.

"The laboratory studies were very compelling," Hagen said. "We were able to make aging blood vessels behave as if they were young again."

According to Balz Frei, professor and director of the Linus Pauling Institute, and co-author on this study, a strength of this approach is that it points the way to use diet to prevent the decline in blood vessel function with age, and to treat it, if necessary, through drugs.

"A compound we're already using showed the ability to lower ceramide levels and improve the cell signaling process, and this compound would be a good starting point for possible drug therapies," Hagen said. "And certain types of diet may help reduce this natural, age-related process."

As is appropriate for many other disease concerns and health conditions, Frei said, a diet that's heavy in fruits and vegetables seems to slow down the loss of blood vessel function. However, the scientists also are doing research with lipoic acid, a powerful antioxidant, that is very promising and may ultimately show it could play a role as a dietary supplement to help address this problem.

This overall process, the researchers said, is linked to a low-grade, chronic inflammation that occurs with aging, in blood vessels and probably many other metabolic functions. Efforts to understand and address these inflammatory processes are some of the most promising areas of chronic disease prevention and treatment, they said.

Original Article

Plaque bomb

2006-11-25T12:12:00.000-05:00

Dentists could soon be out of a job - a "smart bomb" antimicrobial drug
that kills the bacteria that live in plaque could stop tooth decay in
its tracks.

Traditional antibiotics are too indiscriminate to be used against
/Streptococcus mutans/ because they also kill commensal or "friendly"
bacteria, paving the way for other mouth infections. Now Wenyuan Shi of
the University of California, Los Angeles, has created an antimicrobial
that spares commensal bugs.

He linked a peptide that specifically targets /S. mutans/ to the active
region of Novispirin G10, a broad-spectrum antibiotic that destroys
bacterial membranes. The compound killed /S. mutans/ grown in liquid or
as biofilms without harming other oral streptococci (/Antimicrobial
Agents and Chemotherapy/, vol 50, p 3651).

Giving the antimicrobial as a one-off treatment, or at regular
intervals, to kill off /S. mutans/ might enable less harmful bacteria to
colonise its niche, says Shi, making it more difficult for the bug to
regain a toehold. It is unlikely that the bug would develop resistance
to the drug because it would have to go through multiple mutations to
thwart membrane destruction, he adds.

Shi believes that such "selectively targeted antimicrobial peptides" or
STAMPS, might also work against other infections in mixed microbial
environments such as the middle ear, vagina and gastrointestinal tract.

From issue 2578 of New Scientist magazine, 22 November 2006, page 21
Original Article

RNA Activation

2006-11-21T11:50:00.000-05:00

The latest twist on the Nobel prizewinning method of RNA interference, or RNAi, could prove to be a real turn-on. Whereas standard RNAi silences a target gene, switching protein production off, the new technique boosts gene activity, providing a genetic "on" switch.

RNAi can silence genes in two ways. It can block the messenger RNA that is the intermediate between gene and protein and it can also interfere with "promoter" sequences that boost a gene's activity. It was while investigating this second phenomenon that Long-Cheng Li of the University of California, San Francisco, and his colleagues stumbled on the new method, dubbed RNA activation.

Li tried to silence several genes in human cells using short pieces of double-stranded RNA, 21 bases long. But to his surprise, he found that they had precisely the opposite effect (Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.0607015103).

Although the exact mechanism remains unclear, Li's team has already found that it requires a protein called Ago2, which is also involved in the standard RNAi process. Li believes RNA activation could find widespread use, for example in treating cancer by boosting the activity of tumour suppressor genes.

Original Article

Dartmouth researchers identify a gene that enhances muscle performance

2006-11-17T10:55:00.000-05:00

Dartmouth College Office of Public Affairs • Press Release
Posted 11/14/06 • Susan Knapp • (603) 646-3661

A team of researchers, led by scientists at Dartmouth Medical School and Dartmouth College, have identified and tested a gene that dramatically alters both muscle metabolism and performance. The researchers say that this finding could someday lead to treatment for muscle diseases, including helping the elderly who suffer from muscle deterioration and improving muscle performance in endurance athletes.

The researchers report that the enzyme called AMP-activated protein kinase (or AMPK) is directly involved in optimizing muscle activity. The team bred a mouse that genetically expressed AMPK in an activated state. Like a trained athlete, this mouse enjoyed increased capacity to exercise, manifested by its ability to run three times longer than a normal mouse before exhaustion. One particularly striking feature of the finding was the accumulation of muscle glycogen, the stored form of carbohydrates, a condition that many athletes seek by "carbo-loading" before an event or game. The study appears in the Nov. 14 online issue of the American Journal of Physiology: Endocrinology and Metabolism.

"Our genetically altered mouse appears to have already been an exercise program," says Lee Witters, the Eugene W. Leonard 1921 Professor of Medicine and Biochemistry at Dartmouth Medical School and professor of biological sciences at Dartmouth College. "In other words, without a prior exercise regimen, the mouse developed many of the muscle features that would only be observed after a period of exercise training."

Witters, whose lab led the study, explains that this finding has implication for anyone with a muscle disease and especially for the growing proportion of the population that is aging. Deteriorating muscles often make the elderly much more prone to fall, leading to hip and other fractures. According to Witters, there is tremendous interest in the geriatric field to find ways to improve muscle performance.

"We now wonder if it's possible to achieve elements of muscular fitness without having to exercise, which in turn, raises many questions about possible modes of exercise performance enhancement, including the development of drugs that could do the same thing as we have done genetically," he says. "This also might raise to some the specter of 'gene doping,' something seriously being talked about in the future of high-performance athletes."

Witters says that the carbohydrate, glucose, is a major fuel that powers muscles, and this contributes directly to a muscle's ability to repetitively contract during exercise. The activated AMPK in the Dartmouth mouse appears to have increased glycogen content by actually switching on a gene that normally synthesizes liver glycogen.

"The switching on of this liver gene in muscles," he says, "is a shift in the conception of the biochemistry of muscle metabolism, since many enzyme genes are thought to only be active in just one tissue."

Other authors on the paper include Laura Barré, Christine Richardson, and Steven Fiering, all at Dartmouth; Michael Hirshman and Laurie Goodyear of Joslin Diabetes Center in Boston; Joseph Brozinick with Eli Lilly and Company; and Bruce Kemp of the St. Vincent's Institute in Australia.

Have a longer, healthier life

2006-11-15T11:20:00.001-05:00

Avoiding health risk factors in midlife such as smoking, being overweight, excessive drinking and hypertension is associated with a longer and healthier life in men, according to a study in the November 15 issue of JAMA, a theme issue on men's health.

Bradley J. Willcox, M.D., of the Pacific Health Research Institute and Kuakini Medical Center in Honolulu, presented the findings of the study today at a JAMA media briefing on men's health in New York.

Persons alive at age 85 years or older are the fastest-growing age group in most industrialized countries and are among the largest consumers of health care resources. Identifying strategies for remaining healthy, vigorous, and disability-free at older ages has become a major priority, according to background information in the article. Studies with substantial numbers of long-lived participants and characteristics associated with longer survival are rare but essential to identify risk factors for health and survival at older ages.

Dr. Willcox and colleagues examined potential biological, lifestyle, and sociodemographic risk factors present at middle-age to identify risk factors for healthy survival. The study included 5,820 Japanese-American middle-aged men (average age, 54) in the Kuakini Honolulu Heart Program/Honolulu Asia Aging Study. The participants were free of illness and functional impairments and were followed for up to 40 years (1965-2005) to assess overall and exceptional survival. Exceptional survival was defined as survival to a specified age (75, 80, 85, or 90 years) without incidence of 6 major chronic diseases and without physical and cognitive impairment. The diseases were coronary heart disease, stroke, cancer (excluding nonmelanoma skin cancer), chronic obstructive pulmonary disease, Parkinson disease, and treated diabetes. Of the 5,820 original participants, 2,451 participants (42 percent) survived to age 85 years and 655 participants (11 percent) met the criteria for exceptional survival to age 85 years.

The researchers found that high grip strength and avoidance of overweight, hyperglycemia, hypertension, smoking, and excessive alcohol consumption were associated with both overall and exceptional survival. In addition, high education and avoidance of hypertriglyceridemia (elevated triglyceride level) were associated with exceptional survival, and lack of a marital partner was associated with death before age 85 years.

Risk factor models based on cumulative risk factors (survival risk score) suggest that the probability of survival to age 85 years is as high as 69 percent with no risk factors and as low as 22 percent with 6 or more risk factors. The probability of exceptional (healthy) survival to age 85 years was 55 percent with no risk factors but decreased to 9 percent with 6 or more risk factors

"Anthropometric [measurement and study of the human body and its capacities] measures from this study, such as grip strength, suggest that it is important to be physically robust in midlife. This is consistent with theories of aging that suggest that better-built organisms last longer and that physiological reserve is an important determinant of survival," the authors write. This may also be a marker of physical fitness.

"In summary, we have identified several potentially important risk factors for healthy survival in a large group of middle-aged men. These risk factors can be easily measured in clinical settings and are, for the most part, modifiable. This study suggests that common approaches that target multiple risk factors simultaneously, such as avoidance of smoking or hypertension, and approaches that enhance insulin sensitivity, such as maintaining a lean body weight, may improve the probability of better health at older ages. This may be especially important for men, few of whom survive to oldest-old age," the researchers conclude.

Cool down ? you may live longer

2006-11-06T13:52:00.000-05:00

11:20 03 November 2006
NewScientist.com news service
Roxanne Khamsi

The refrigerator is used to lengthen the life of your food, and a new study suggests a similar principle could prolong your life, too.

Researchers have found that lowering the body temperature of mice by just 0.5°C extends their lifespan by around 15%. In the future, people might be able to take a drug to achieve a similar effect on body temperature and enjoy a longer life, they say.

The only previously proven method of significantly increasing the lifespan of an animal has been through a restricted calorie diet.

Bruno Conti at Scripps Research Institute in La Jolla, California, US, and colleagues designed genetically engineered mice with a specific brain-cell defect in a region called the lateral hypothalamus. The defect forces brain cells into "overdrive", causing the region to heat up and become warmer than in a normal mouse.
Female benefit

Since, in mice, the lateral hypothalamus sits just 0.8 millimetres away from the brain’s body-temperature-controlling thermostat – called the preoptic area – it was tricked into thinking its body temperature was too high, causing the mouse to cool down.

The average body temperature of the genetically engineered mice was about 0.6°C lower than that of their control counterparts.

Even this small decrease in body temperature appeared to have a noticeable effect on lifespan, extending their lives by 12% to 20%. And the decrease in body temperature extended the lifespan of female mice more than male mice, the team found, although they are unsure why.
Free radicals

Caloric restriction, another method shown to extend animals’ lives, also causes a decrease in body temperature, Conti notes. In his study, both groups of mice ate about the same amount. In fact, the genetically engineered male mice ended up about 10% heavier than the normal male mice.

Conti says the findings show it is the lowering of body temperature – and not necessarily the consumption of fewer calories – that plays the most important role in extending lifespan.

This may be because the body burns less fuel when it is at a lower temperature, which results in the production of fewer free-radical compounds that damage cells and promote the wear and tear of ageing. Previous studies have shown that worms and fish that have decreased body temperatures live longer.

Conti says that in the future people might be able to take a drug that specifically targets the preoptic “thermostat” area in their brains to trick the body into cooling down slightly. Coming up with such a drug “will be very challenging”, but he hopes it would allow people to live longer without cutting back on the calories.

Journal reference: Science (DOI: 10.1126/science.1132191)

Resveratrol

2006-11-02T07:56:00.001-05:00

http://www.nature.com/nature/journal/vaop/ncurrent/full/nature05354.html

Resveratrol (3,5,4'-trihydroxystilbene) extends the lifespan of diverse species including Saccharomyces cerevisiae, Caenorhabditis elegans and Drosophila melanogaster. In these organisms, lifespan extension is dependent on Sir2, a conserved deacetylase proposed to underlie the beneficial effects of caloric restriction. Here we show that resveratrol shifts the physiology of middle-aged mice on a high-calorie diet towards that of mice on a standard diet and significantly increases their survival. Resveratrol produces changes associated with longer lifespan, including increased insulin sensitivity, reduced insulin-like growth factor-1 (IGF-I) levels, increased AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha) activity, increased mitochondrial number, and improved motor function. Parametric analysis of gene set enrichment revealed that resveratrol opposed the effects of the high-calorie diet in 144 out of 153 significantly altered pathways. These data show that improving general health in mammals using small molecules is an attainable goal, and point to new approaches for treating obesity-related disorders and diseases of ageing.

Silicon retina mimics biology for a clearer view

2006-10-20T11:59:00.001-04:00

20 October 2006
NewScientist.com news service
Tom Simonite

A silicon chip that faithfully mimics the neural circuitry of a real retina could lead to better bionic eyes for those with vision loss, researchers claim.

About 700,000 people in the developed world are diagnosed with age-related macular degeneration each year, and 1.5 million people worldwide suffer from a disease called retinitis pigmentosa. In both of these diseases, retinal cells, which convert light into nerve impulses at the back of the eye, gradually die.

Most artificial retinas connect an external camera to an implant behind the eye via a computer (see 'Bionic' eye may help reverse blindness). The new silicon chip created by Kareem Zaghloul at the University of Pennsylvania, US, and colleague Kwabena Boahen at Stanford University, also in the US, could remove the need for a camera and external computer altogether.

The circuit was built with the mammalian retina as its blueprint. The chip contains light sensors and circuitry that functions in much the same way as nerves in a real retina – they automatically filter the mass of visual data collected by the eye to leave only what the brain uses to build a picture of the world.
Fully implanted

"It has potential as a neuroprosthetic that can be fully implanted," Zaghloul told New Scientist. The chip could be embedded directly into the eye and connected to the nerves that carry signals to the brain's visual cortex.

To make the chip, the team first created a model of how light-sensitive neurons and other nerve cells in the retina connect to process light. They made a silicon version using manufacturing techniques already employed in the computer chip industry.

Their chip measures 3.5 x 3.3 millimetres and contains 5760 silicon phototransistors, which take the place of light-sensitive neurons in a living retina. These are connected up to 3600 transistors, which mimic the nerve cells that process light information and pass it on to the brain for higher processing. There are 13 different types of transistor, each with slightly different performance, mimicking different types of actual nerve cells.

"It does a good job with some of the functions a real retina performs," says Zaghloul. For example, the retina chip is able to automatically adjust to variations in light intensity and contrast. More impressively, says Patrick Deganeer, a neurobionics expert at Imperial College London, UK, it also deals with movement in the same way as a living retina.
Changing scene

The mammalian brain only receives new information from the eyes when something in a scene changes. This cuts down on the volume of information sent to the brain but is enough for it to work out what is happening in the world.

The retina chip performs in the same way. The lowest image (right) shows how this allows it to extract useful data from a moving face.

As well as having the potential to help humans with damaged vision, future versions of the retina chip could help robots too, adds Deganeer. "If you can perform more processing in hardware at the front end you reduce demand on your main processor, and could cut power consumption a lot," he explains.

Zaghloul and Boahen are currently concentrating on reducing the size and power consumption of the retina chip before considering clinical trials.

Journal reference: Journal of Neural Engineering (vol 3, p 257)

MIT material stops bleeding in seconds

2006-10-10T12:32:00.001-04:00

Work could significantly impact medicine

CAMBRIDGE, Mass.--MIT and Hong Kong University researchers have shown that some simple biodegradable liquids can stop bleeding in wounded rodents within seconds, a development that could significantly impact medicine.
When the liquid, composed of protein fragments called peptides, is applied to open wounds, the peptides self-assemble into a nanoscale protective barrier gel that seals the wound and halts bleeding. Once the injury heals, the nontoxic gel is broken down into molecules that cells can use as building blocks for tissue repair.
"We have found a way to stop bleeding, in less than 15 seconds, that could revolutionize bleeding control," said Rutledge Ellis-Behnke, research scientist in the MIT Department of Brain and Cognitive Sciences.
This study will appear in the online edition of the journal Nanomedicine on Oct. 10 at http://www.nanomedjournal.com/inpress. It marks the first time that nanotechnology has been used to achieve complete hemostasis, the process of halting bleeding from a damaged blood vessel.
Doctors currently have few effective methods to stop bleeding without causing other damage. More than 57 million Americans undergo nonelective surgery each year, and as much as 50 percent of surgical time is spent working to control bleeding. Current tools used to stop bleeding include clamps, pressure, cauterization, vasoconstriction and sponges.
In their experiments on hamsters and rats, the MIT and HKU researchers applied the clear liquid containing short peptides to open wounds in several different types of tissue - brain, liver, skin, spinal cord and intestine.
"In almost every one of the cases, we were able to immediately stop the bleeding," said Ellis-Behnke, the lead author of the study.
Earlier this year, the same researchers reported that a similar liquid was able to partially restore sight in hamsters that had had their visual tract severed. In that case, the self-assembling peptides served as an internal matrix on which brain cells could regrow.
While experimenting with the liquid during brain surgery, the researchers discovered that some of the peptides could also stop bleeding, Ellis-Behnke said. He foresees that the material could be of great use during surgery, especially surgery that is done in a messy environment such as a battlefield. A fast and reliable way to stop bleeding during surgery would allow surgeons better access and better visibility during the operation.
"The time to perform an operation could potentially be reduced by up to 50 percent," said Ellis-Behnke.
Unlike some methods now used for hemostasis, the new materials can be used in a wet environment. And unlike some other agents, it does not induce an immune response in the animals being treated.
When the solution containing the peptides is applied to bleeding wounds, the peptides self-assemble into a gel that essentially seals over the wound, without harming the nearby cells. Even after excess gel is removed, the wound remains sealed. The gel eventually breaks down into amino acids, the building blocks for proteins, which can be used by surrounding cells.
The exact mechanism of the solutions' action is still unknown, but the researchers believe the peptides interact with the extracellular matrix surrounding the cells. "It is a completely new way to stop bleeding; whether it produces a physical barrier is unclear at this time," Ellis-Behnke said.
The researchers are confident, however, that the material does not work by inducing blood clotting. Clotting generally takes at least 90 seconds to start, and the researchers found no platelet aggregation, a telltale sign of clotting.
Other MIT researchers who are co-authors on the paper are Gerald Schneider, professor of brain and cognitive sciences, and Shuguang Zhang, associate director of MIT's Center for Biomedical Engineering. Collaborators at the University of Hong Kong Li Ka Shing Faculty of Medicine, Department of Anatomy, include Yu-Xiang Liang, David Tay, Wutian Wu, Phillis Kau and Kwok-Fai So, an MIT alumnus.

Rescuing injured hearts by enhancing regeneration

2006-10-10T10:35:00.001-04:00

Animal study suggests novel way to reverse heart-attack damage

Using a two-drug approach, researchers at Children's Hospital Boston have demonstrated that it may be possible to rescue heart function after a heart attack and protect the heart from scarring. Working with rats, they combined an agent that overcomes a natural inhibitor of cell division with a naturally occurring growth factor that encourages blood vessel growth (angiogenesis). Together, these two agents enabled heart-muscle cells to multiply and the heart to regain its function after a simulated myocardial infarction. The study will appear in the October 17 issue of the Proceedings of the National Academy of Sciences (posted online during the week of October 9).
Normally, after a heart attack, the damaged heart muscle cannot grow back and is instead replaced by scar tissue. Excessive scarring can impair the heart's pumping capacity and can lead to life-threatening arrhythmias. Heart-muscle cells (cardiomyocytes) normally cannot replicate in mammals, a major obstacle to regeneration. However, in a paper last year, Felix Engel, PhD, and Mark Keating, MD, in the Department of Cardiology at Children's Hospital Boston, showed that they could coax cardiomyocytes to multiply in a petri dish by inhibiting an enzyme known as p38 MAP kinase, which normally suppresses cardiomyocyte replication. [See: here]
Engel and Keating (Keating is now at the Novartis Institute for BioMedical Research) now build on this finding. They studied 120 rats, some with simulated heart attacks. After the injury, the animals were randomly assigned to receive injections with a p38 MAP kinase inhibitor alone, the angiogenesis stimulator FGF1 alone, both agents together, or saline (placebo) for four weeks. Three months later, rats that had received both FGF1 and the p38 MAP kinase inhibitor had markedly improved heart function, as measured on echocardiograms: their hearts pumped almost as well as the hearts of uninjured rats. They also had reduced thinning of the cardiac wall and the least amount of scarring.
Rats receiving only the p38 MAP kinase inhibitor had increased proliferation of cardiomyocytes, but no longer had improved heart function at three months. Those receiving only FGF1 maintained their functional improvement, but did not show as much cell proliferation as those receiving the p38 MAP kinase inhibitor. Rats receiving both agents had the greatest improvements in both cell proliferation and heart function.
The findings suggest that getting cardiomyocytes to replicate is not enough to rescue heart function, but that angiogenesis is also needed, Engel says.
"Regeneration is not just making more cardiomyocytes," he says. "Cardiomyocytes need a blood supply and oxygen to survive. FGF1 did not have a great effect on cell proliferation, but we found it was providing a new blood supply. If you just inhibit p38 MAP kinase, you don't get blood vessels."
Two important steps are needed to turn these findings into a treatment, Engel says. First is to show that the treatment works when not given immediately after the heart attack, since many people sustain progressive damage to their hearts from repeated minor infarctions. In this study, rats were treated soon after injury.
Second is the need to develop a safe delivery method. Because FGF1 stimulates angiogenesis, it has the potential for serious side effects if it goes to places other than the heart, possibly promoting tumor growth, for example. And the p38 MAP kinase inhibitor has been shown to damage the liver.
"Every treatment trying to induce proliferation of cardiomyocytes also carries a risk of inducing tumor growth, and thus you have to limit the time and location of treatment," Engel adds.
One possibility is to inject smaller doses of the agents into the damaged area of the heart in gel form, or instill them through a catheter, so that they would remain in the heart and be released slowly over time. Engel and colleagues recently reported another compound that stimulates cardiomyocyte proliferation (Chemistry and Biology, Sept. 2006), and others are under investigation.
"In the end, we'd like a treatment that could be given systemically," Engel says.

Blood cells linked to heart attacks, other inflammatory diseases

2006-10-09T09:29:00.000-04:00

Cox-2 production initiated by cellular cross talk

SALT LAKE CITY -- It's a case of miscommunication with catastrophic consequences.

Two human blood cells that help fight blood loss, infection, and inflammation are responsible as well for starting a series of molecular events that results in overproduction of Cox-2, an enzyme involved in heart attack, stroke, atherosclerosis, and other inflammatory diseases.

The finding by researchers at the University of Utah and University of South Carolina means scientists may be able to develop drugs to prevent or lessen the severity of inflammatory diseases, such as atherosclerosis and heart attack. Discovery of the signaling mechanism will be invaluable in sorting out the roles Cox-2 plays in those diseases, according to Guy A. Zimmerman, M.D., University of Utah School of Medicine professor of internal medicine, senior author of the study detailing the research.

"This discovery has immediate clinical relevance," said Zimmerman, director of the medical school's Program in Human Molecular Biology and Genetics. "This opens the potential of developing medications for both the prevention of long-term atherosclerosis (clogged arteries) and the acute events of heart attack."

The study, reported in the Journal of Clinical Investigation online, also was led by Dan A. Dixon, a former member of Zimmerman's lab now at South Carolina.

The researchers identified a biochemical signaling pathway between human blood platelets, cells essential for blood clotting, and monocytes, white blood cells the body makes to fight inflammation and infection. But, according to Zimmerman, the biological systems involved in blood clotting and inflammation also are related to a host of human diseases.

The Utah and South Carolina researchers discovered that the blood platelet signals the monocyte two times, triggering production of Cox-2, an enzyme that helps regulate inflammation. But when blood platelets and monocytes get their signals crossed, it can lead to overproduction of the enzyme and result in cardiovascular diseases that strike and kill millions of people worldwide.

Zimmerman compares the signaling between blood platelets and monocytes to a pair of molecular control switches that turn Cox-2 production on and off. "It's a mechanism for precise control of Cox-2 production," he said. "But if one of the switches is turned on too high or low, it can lead to inappropriate production of Cox-2 in disease."

The first signal from the platelet tells the monocyte to turn on the gene that provides the instructions necessary to make Cox-2. These instructions are carried in small molecule called messenger RNA. When the blood platelet signals the monocyte, the cell decodes the instructions from the Cox-2 gene in a process called transcription. This results in production of messenger RNA that specifically codes for Cox-2. After the messenger RNA is transcribed, the blood platelet then sends a second signal to the monocyte that regulates stability of the Cox-2 messenger RNA and further decoding of the genetic information in a process called translation.

This results in production of the Cox-2 protein and controls how much, and at what time point, it is produced.

Drugs called non-steroidal anti-inflammatory agents, which inhibit production of Cox-2 and reduce inflammation, are some of the most widely used medications in the world for arthritis and other inflammatory diseases. But some of these drugs, also called Cox-2 inhibitors, such as Vioxx, increase the chance of heart attack.

Identifying the signaling mechanism between blood platelets and monocytes makes it possible to develop new drugs to modify Cox-2 production. "Knowing these steps gives you an initial blueprint about how to modify Cox-2," Zimmerman said. Understanding this mechanism may enable researchers to develop drugs that help people during a heart attack, or prevent heart attack, stroke or other inflammatory diseases.

AGE Crosslink breaker

2006-10-04T23:01:00.000-04:00

Alagebrium is the only A.G.E. Crosslink Breaker in advanced human testing. The compound has demonstrated promising results in several Phase 2 human clinical trials and is being developed initially for cardiovascular and vascular diseases. Results to date suggest that alagebrium may be a novel therapy for a number of conditions that occur as a result of myocardial or vascular alterations associated with aging or diabetes. Preliminary evidence suggests that the compound is able to modify both the structure and function of the left ventricle (main pumping chamber of the heart) consistent with a partial reversal of pathology. Similarly, alagebrium has been shown to improve the reactivity and function of the arterial system. In addition, in all clinical testing to date, the compound has demonstrated a clean safety profile.

Archon X PRIZE for Genomics

2006-10-04T22:12:00.000-04:00

On October 4, 2006, the X PRIZE Foundation announced the launch of its second prize — the Archon X PRIZE for Genomics. The $10 million cash prize has been created to revolutionize the medical world. The launch was attended by visionaries and entrepreneurs from around the globe who recognize the significance and impact that the Archon X PRIZE for Genomics will have on the fields of medicine and research.

Cloned mice created from fully differentiated cells, a milestone in cloning research

2006-10-03T13:28:00.001-04:00

New research dismisses the notion that adult stem cells are necessary for successful animal cloning, proving instead that cells that have completely evolved to a specific type not only can be used for cloning purposes, but they may be a better and more efficient starting point. As proof, researchers report they created two mouse pups from a type of blood cell that itself is incapable of dividing to produce a second generation of its own kind.
This is the first demonstration that an animal can be derived directly from a fully differentiated cell, report lead researchers Xiangzhong (Jerry) Yang, Ph.D., of the University of Connecticut, and Tao Cheng, M.D., of the University of Pittsburgh, in the journal Nature Genetics.

Moreover, they say results of their studies provide compelling evidence that Dolly the sheep and other mammals cloned by somatic cell nuclear transfer were most likely derived from fully differentiated cells, not adult stem cells, as most have argued in the nine years since Dolly was first created. Because stem cells have the ability to self-renew and differentiate into any specialized cell type, they have been heralded for their promise for treating a variety of diseases and conditions. Yet, even for cloning of an embryo to the blastocyst stage, from which embryonic stem cells can be generated, adult stem cells have yielded disappointing results, with success rates in the range of 1 to 5 percent.

Somatic cell nuclear transfer (SCNT), the scientific term for cloning, involves creating an embryo by using a nucleus that's been removed from a somatic cell – any cell other than a reproductive cell – and transferring it into an unfertilized egg that has had its chromosomes removed. Because the resulting new embryo contains the entire genome of the donor somatic cell it is an identical copy. This cloned embryo is then implanted into a surrogate mother, and, if the process is successful, is carried to term.

In their studies, the researchers compared the efficiency for cloning mice using a fully differentiated blood cell called a granulocyte with its ancestor cells at different stages: hematopoietic stem cells, which are found in bone marrow and give rise to all red and white blood cells, and progenitor cells. Granulocytes are well characterized white blood cells unique for their segmented nuclei and the numerous granules in the cells' cytoplasm.

Surprisingly, the granulocytes were the most efficient donor cells for nuclear transfer among the different lineage cells, with 35 to 39 percent becoming a blastocyst, an early embryo consisting of about 100 to 150 cells, compared to 11 percent for the progenitor cells and only 4 percent for the stem cells. Only the granulocytes were able to produce two live cloned pups, although both died within a few hours of birth. As a control, the researchers performed nuclear transfer using embryonic stem cells; 49 percent developed to the blastocyst stage and 18 cloned pups were born.

"Our results clearly demonstrate that there is no apparent advantage in using either adult stem cells or progenitor cells over fully differentiated cells as nuclear donors. To the contrary, we found that cloned pups can be produced from adult, fully differentiated somatic cells, a conclusion that goes against popular opinion and current hypotheses," says Dr. Yang, animal science professor, director of the University of Connecticut's Center for Regenerative Biology and co-corresponding author of the study.

"Even we were surprised to find fully differentiated cells were more efficient for cloning, because granulocytes are not capable of dividing. In fact, we repeated our experiments six times just to be sure. Now we can say with near certainty that a fully differentiated cell such as a granulocyte retains the genetic capacity for becoming like a seed that can give rise to all cell types necessary for the development of an entire organism," adds co-corresponding author Dr. Cheng, associate professor of radiation oncology at the University of Pittsburgh School of Medicine and director of stem cell biology and co-leader of the cancer stem cell program at the University of Pittsburgh Cancer Institute.

Previous attempts by scientists to produce animal clones directly from fully differentiated B cells, T cells and neurons had failed beyond the blastocyst stage. Only with a second step that involved combining the blastocyst with a fertilized embryo, which produces what biologists call a chimera, or by performing another nuclear transfer using the embryonic stem cells derived from these blastocysts, could "cloned" pups be produced. Even so, other researchers have countered these are not bona fide clones because they possess chromosomes that are not identical to those of the original donor nucleus.

Since Dolly, animal cloning using adult cells has been accomplished in more than a dozen mammalian species, but the process is highly inefficient. Even if the reconstructed eggs survive to the blastocyst stage, only a handful, at most, of these result in live young when implanted into a female.

Many have attributed cloning's limited success to a theory that clones must be derived from adult stem cells, which reside in a specific area of each tissue and remain quiescent until they are activated by the presence of disease or tissue injury. Yet, if this were true, Drs. Yang and Cheng point out, the results of their studies would have found the adult stem cells to be more efficient than the other, more differentiated cells.

"Of the 1,828 nuclear transfers we performed with stem cells, very few could develop to the blastocyst stage and not one clone was produced. With such odds, it's hard to believe that Dolly and other cloned animals could have possibly been derived from adult stem cells. Much more likely is that these animals were derived from fully differentiated tissue cells," Dr. Yang argues.

While more research is needed to determine if what they found with hematopoietic cells will be true for cells of other tissue types, the investigators say their current studies may have important implications for regenerative medicine, since the findings suggest the potential of adult stem cells in this arena may be more limited than previously thought. However, of particular interest to Dr. Cheng is the relevance of their findings to cancer stem cell research.

"An interesting question to me is whether SCNT can play a role in understanding or even reprogramming the behavior of cancer stem cells. Such studies may potentially reveal a new set of molecular targets that could aid in the treatment of cancer," says Dr. Cheng.

Source: University of Pittsburgh

This news is brought to you by PhysOrg.com

Human embryonic stem cells display a unique pattern of chemical modification to DNA

2006-09-26T17:01:00.000-04:00

Study suggests additional hurdles to therapeutic cloning may lie ahead

San Diego, Calif. -- Scientists from the Burnham Institute for Medical Research (BIMR) and Illumina Inc., in collaboration with stem cell researchers around the world, have found that the DNA of human embryonic stem cells is chemically modified in a characteristic, predictable pattern. This pattern distinguishes human embryonic stem cells from normal adult cells and cell lines, including cancer cells. The study, which appears online today in Genome Research, should help researchers understand how epigenetic factors contribute to self-renewal and developmental pluripotence, unique characteristics of human embryonic stem cells that may one day allow them to be used to replace diseased or damaged cells with healthy ones in a process called therapeutic cloning.

Embryonic stem cells are derived from embryos that are undergoing a period of intense cellular activity, including the chemical addition of methyl groups to specific DNA sequences in a process known as DNA methylation. The methylation and demethylation of particular DNA sequences in the genome are known to have profound effects on cellular behavior and differentiation. For example, DNA methylation is one of the critical epigenetic events leading to the inactivation of one X chromosome in female cells. Failure to establish a normal pattern of DNA methylation during embryogenesis can cause immunological deficiencies, mental retardation and other abnormalities such as Rett, Prader-Willi, Angelman and Beckwith-Wiedemann syndromes.

Until recently, DNA methylation could only be studied one gene at a time. But a new microarray-based technique developed at Illumina enabled the scientists conducting this new study to simultaneously examine hundreds of potential methylation sites, thereby revealing global patterns. "Analyzing the DNA methylation pattern of hundreds of genes at a time opens a new window for epigenetic research," says Dr. Jian-Bing Fan, director of molecular biology at Illumina. "Exciting insights into development, aging, and cancer should come quickly from understanding global patterns of DNA methylation."

To examine global DNA methylation patterns in human embryonic stem cells, the researchers analyzed 14 human embryonic stem cell lines from diverse ethnic origins, derived in several different labs, and maintained for various times in culture. They tested over 1500 potential methylation sites in the DNA of these cells and in other cell types and found that the embryonic stem cells shared essentially identical methylation patterns in a large number of gene regions. Furthermore, these methylation patterns were distinct from those in adult stem cells, differentiated cells, and cancer cells.

"Our results suggest that therapeutic cloning of patient-specific human embryonic stem cells will be an enormous challenge, as nuclei from adult cells will have to be epigenetically reprogrammed to reflect the specific DNA methylation signature of normal human embryonic stem cells," explains Dr. Jeanne Loring, co-director of the stem cell center at BIMR. "This reinforces the need for basic research directed at understanding the fundamental biology of human embryonic stem cells before therapeutic uses can be considered."

Peter Thiel puts his weight behind Dr. Aubrey de Grey ?s engineering blueprint

2006-09-18T13:03:00.000-04:00

San Francisco – Peter A. Thiel, co-founder and former CEO of online payments system PayPal, Founder and Managing Member of Clarium Capital Management, a San Francisco-based hedge fund, and angel investor in social networking site Facebook, has announced his pledge of $3.5 Million to support scientific research into the alleviation and eventual reversal of the debilities caused by aging, to be conducted under the auspices of the Methuselah Foundation, a charity co-founded and Chaired by Dr. Aubrey de Grey.
Mr. Thiel commented "Rapid advances in biological science foretell of a treasure trove of discoveries this century, including dramatically improved health and longevity for all. I’m backing Dr. de Grey, because I believe that his revolutionary approach to aging research will accelerate this process, allowing many people alive today to enjoy radically longer and healthier lives for themselves and their loved ones.
Mr. Thiel will donate a total of $500,000 over the next three years to fund pilot research projects intended to deliver early stage validation of the “SENS” approach to combating the debilitation caused by aging.
Additionally, from now until the end of 2009, Mr. Thiel promises to match every Dollar donated to the Methuselah Foundation for SENS research with a 50 cent matching contribution from himself, up to a maximum of $3 Million of matching funds.
Dr. de Grey said “I am extremely grateful to Peter for his bold and visionary initiative. I have been working with leading biologists and biochemists around the world in identifying promising research projects, and with this generous donation we will go to work straightaway.”

MitoSENS

2006-09-13T13:54:00.001-04:00

About MitoSENS

Mitochondria are a component of cells that perform cellular respiration. That is to say, they react oxygen with nutrients from our free radicalfood to produce water, carbon dioxide, and useable energy (in the form of ATP). A side effect of this process is the production of reactive chemical byproducts that damage nearby components of the cell. Mitochondria are unique in that they have their own DNA (mtDNA), separate from the nucleus. Being at the site of cellular respiration, the mtDNA is vulnerable to its reactive byproducts. Worse yet, the mitochondria's capacity for repairing DNA damage is much more limited than that of the nucleus. Mutations to the mtDNA inevitably accumulate leading to dysfunction of mitochondria, and contributing to aging of the organism. The goal of MitoSENS is to obviate mtDNA mutations by expressing the mtDNA genes from the nucleus.

Fortunately, we would be completing a process that evolution has already started.

The mitochondrial genome originally had thousands of genes, but evolution has reduced it to a mere 13 (protein encoding) genes in humans. By studying how nature transfered expression of other genes from the mitochondria to the nucleus, we can identify the necessary steps to transfer the remaining 13 genes (in humans).

MitoSENS research is currently being conducted in the lab of Ian Holt at Cambridge University. To learn more about the MitoSENS strategy from its originator and Methuselah Foundation chairperson Aubrey de Grey, see the SENS website here (laymans terms) or here (technical).
The Research Team

Mark Hamalainen is a researcher for the Methuselah Foundation and a PhD Candidate at Cambridge University. He has previously worked on the LysoSENS project and is now focusing on MitoSENS.

Questions and Contact

Any questions or comments on MitoSENS research can be directed to mark.hamalainen@gmail.com

Switching off Aging in Stem Cells

2006-09-07T08:40:00.001-04:00

From Howard Hughes Medical Institute
A single molecular switch plays a central role in inducing stem cells in the brain, pancreas, and blood to lose function as they age, researchers have found. Mice lacking that switch show considerably reduced aging-related decline in stem cell function and tissue regeneration.

“People tend to think that old tissues have less regenerative capacity because they are wearing out,” said Sean J. Morrison, a Howard Hughes Medical Institute investigator at the University of Michigan who led the study of the switch's role in the brain. “This work shows that they are not just wearing out; they are actively shutting themselves down.”

While the finding could ultimately lead to drugs to slow or reverse degeneration in the brain and other tissues, the researchers cautioned such treatments would have to be balanced against the chance of increasing cancer risk in patients. Stem cells are the immature progenitor cells that are the continuing self-renewing source of mature, differentiated cells in the body.

Morrison's study was published online September 6, 2006, in Nature, ahead of publication in the journal's print version, along with two other studies from independent research teams that studied how a protein called inhibitor of cyclin-dependent kinase 4A, or p16^INK4a, contributes to stem cell decline. The other papers reported studies of the gene's role in stem cell decline in insulin-producing pancreatic islet cells and hematopoietic stem cells, which generate blood cells. Those studies were headed, respectively, by Norman Sharpless of the University of North Carolina at Chapel Hill and David Scadden of Harvard University.

“Before this work, p16^INK4a was thought of only as a gene that inhibited cancer formation by inducing senescence in the cell,” said Morrison. “The idea was that it wasn't expressed in normal tissues, and therefore probably didn't have a physiological role but only came on when something went wrong in the cell.”

However, said Morrison, studies in Sharpless's laboratory found that the gene becomes increasingly active as tissues age. “That started us thinking that maybe this gene is part of why old tissues have less stem cell activity and less regenerative capacity, for example taking longer to heal,” said Morrison. “In our lab, for example, we've found that the brain makes fewer neurons with age, but the molecular mechanism for that effect was not known.”

Morrison and his colleagues followed stem cell activity in the brains of normal mice as they aged. The researchers analyzed a particular area of the forebrain, the subventricular zone, known to be an important center of neuronal production, called neurogenesis, in adults. The other two research teams studied pancreatic islet cells and hematopoietic stem cells for the same reason - that they are a constant source of new cells in the adult.

Morrison and his colleagues found that stem cell number and self-renewal function, as well as neurogenesis, declined with age in the mice. But they found that during aging, p16^INK4a gene activity increased.

However, in genetically engineered mice that were deficient in p16^INK4a, stem cell function and neuronal production were enhanced in old but not young mice as compared to normal mice. “We didn't turn an old brain into a young brain by deleting p16^INK4a, but the deficient mice did show significantly increased progenitor cell function and neurogenesis with age, compared to normal mice,” said Morrison. “This tells us that p16^INK4a is not the whole story, although it's an important part, and that other genes also regulate the aging process.”

Morrison and his colleagues also found evidence that the gene does not play the same role in other neural tissues. “There are different kinds of stem cells in different regions of the brain, and some of those stem cells are more sensitive to factors like p16^INK4a than others,” said Morrison. p16^INK4a deficiency did not prevent the atrophy of the cortex that normally occurs with aging, they found. Nor did the deficiency prevent loss of function in another brain region, the hippocampus, that is also a center for neurogenesis in adults. The researchers also analyzed peripheral nerve cells in the gut and found that p16^INK4a did not prevent loss of stem cell function there. “There are probably other factors that are important for aging of the hippocampus and the peripheral nervous system,” Morrison noted.

Nevertheless, he said, the discovery of the central role of p16^INK4a is highly significant. “I think if you asked before these studies whether you could delete a single gene and rescue stem cell function in multiple tissues, and neurogenesis in an old brain, many people would have said that aging is such a complex phenomenon that you would not get a significant effect,” he said.

Morrison theorized that p16^INK4a is a suppressor of stem cell function that evolved as part of the regulatory machinery that also includes proto-oncogenes that encourage cell proliferation. “We are all evolutionarily selected to, on the one hand, maintain regenerative capacity of our tissues through adult life so that we can repair our cells and survive injuries — while on the other hand, limit proliferation in our tissues with age, so cells don't divide out of control, causing cancers,” he said. “And the way that we achieve that balance is by having proto-oncogenes that promote proliferation come into balance with tumor suppressor genes that inhibit proliferation. This work shows one way that this balance changes with age.

“While these tumor suppressor mechanisms don't even exist during fetal development, where cells must divide rapidly, it makes sense that they become stronger in old age, when we are more at risk of getting a cancer,” said Morrison. “So, the benefit is that genes like p16 allow us to get older before we get cancer, but the bad news is that they make us lose function with age.”

Research that will change your life!

2006-08-03T12:02:00.000-04:00

The evidence that caloric restriction extends life in animal species inspires thousands to adopt calorie restriction as a way of life. But unlike animals in research studies that have clearly defined diet parameters and protocols, humans have many ideas about how caloric restriction should be practiced.

If you are reading this, most likely you are very serious about functioning at your peak. Nothing is more precious.

[...]

That’s why the Calorie Restriction Society has initiated a milestone study that will correlate human calorie restrictors’ genetic expression and cell signaling indicators to clinical markers. Once these correlations are established, serious longevists will be equipped with easy-to-run clinical tests that indicate how well their regimens are working.

Revolutionary Stem Cell Transplant in Athens a World First

2006-08-03T11:52:00.000-04:00

Athens News Agency
26 July 2006

Revolutionary stem-cell transplant in Athens a world first A baby-girl born in Athens last week will become the donor of stem cells taken from the umbilical cord that will be transplanted to her 4-year-old brother suffering from chronic granulomatous disease, a congenital heterogeneous immunodeficiency disorder resulting from the inability of phagocytes to kill intested microbes, resulting in increased susceptibility to severe infectionsthat ultimately leads to early death.
[...]

Scientists Say They ?ve Found a Code Beyond Genetics in DNA

2006-08-01T07:04:00.000-04:00

Researchers believe they have found a second code in DNA in addition to the genetic code.

The genetic code specifies all the proteins that a cell makes. The second code, superimposed on the first, sets the placement of the nucleosomes, miniature protein spools around which the DNA is looped. The spools both protect and control access to the DNA itself.

The discovery, if confirmed, could open new insights into the higher order control of the genes, like the critical but still mysterious process by which each type of human cell is allowed to activate the genes it needs but cannot access the genes used by other types of cell.

[...]

By NICHOLAS WADE

White Blood Cells From Cancer-resistant Mice Cure Cancers In Ordinary Mice

2006-07-31T20:57:00.000-04:00

Original here.
The original studies on the cancer-resistant mice -- reported in 2003 -- showed that such resistance could be inherited, which had implications for inheritance of resistance in humans, said Mark C. Willingham, M.D., a pathologist and co-investigator. "This study shows that you can use this resistant-cell therapy in mice and that the therapy works. The next step is to understand the exact way in which it works, and perhaps eventually design such a therapy for humans."

The cancer-resistant mice all stem from a single mouse discovered in 1999. "The cancer resistance trait so far has been passed to more than 2,000 descendants in 14 generations," said Cui, associate professor of pathology. It also has been bred into three additional mouse strains. About 40 percent of each generation inherits the protection from cancer.

The original group of cancer-resistant mice, also described in Proceedings of the National Academy of Sciences, successfully fought off a range of virulent transplanted cancers.

"Now we know that we can take white blood cells from this strange mouse and put them into a normal mouse and these cells will still kill cancers," said Willingham, professor of pathology and head of the Section on Tumor Biology. "This is therapy in a mouse that does not have this magical genetic inheritance."

Johns Hopkins researchers find link between cell's energy use and genome health

2006-07-24T07:46:00.000-04:00

Another possible link between diet and aging

While studying how a cell keeps its genetic material intact, scientists at Johns Hopkins got busy alternately knocking out two catalysts vital to managing a yeast cell's energy. They discovered to their complete surprise that the removal of one of them led the cell to turn off 70 percent of its 5,000 genes and die.

"We were completely unprepared for such a dramatic event," says Jef Boeke, Ph.D., Sc.D., a professor of molecular biology and genetics at Hopkins and author of the study. "We've never seen anything that can turn off that many genes in a cell at once."

[...]

Further analysis with high-power microscopes revealed that this second enzyme, Asc2p, was residing - unexpectedly -- in the part of the cell housing its genetic material - its chromosomes - rather than in the part of the cell - the mitochondria -- that harvests energy from sugar.

But why would an enzyme involved in generating energy live in the "wrong" part of the cell? A closer look at the chromosomal and non-chromosomal parts of the cell showed that although the enzyme itself is found only in the former, the chemical made by it is found in both places

[...]

When the research team removed the enzyme Asc2p that makes acetyl-CoA from yeast cells, they predicted, if they were right about why the enzyme and its chemical product are found near chromosomes, that the chromosomes would have less acetyl-CoA. Less acetyl-CoA, they reasoned, could cause DNA to be more tightly wrapped in chromosomes, and this might lead to genes being turned off. That is exactly what they found when they looked at the more than 5,000 genes in the yeast cells lacking this enzyme. More than 70 percent of them were indeed turned off.

According to Boeke, other studies have shown that reducing the number of calories a yeast cell "eats" not only can affect chromosomes, but also increase lifespan, allowing the yeast to live longer, an observation that fits their findings. .

Cryonics

2006-07-14T15:34:00.000-04:00

Things on the cryonics front are looking good. With the advances Alcor has made in cryonics using their cryoprotectant that becomes glassy instead of cryatalline, and this new, we'll be looking real good before long

[...]

Long the domain of transhumanist nut-jobs, cryogenic suspension may be just two years away from clinical trials on humans (presuming someone can solve the sticky ethical problems). Trauma surgeons can’t wait – saving people with serious wounds, like gunshots, is always a race against the effects of blood loss. When blood flow drops, toxins accumulate; just five minutes of low oxygen levels causes brain death.

Chill a body, though, and you change the equation. Metabolism slows, oxygen demand dives, and the time available to treat the injury stretches. Alam has suspended 200 pigs for an hour each, and although experimental protocol calls for different levels of care for each pig, the ones that got optimal treatment all survived.

Slow-frozen people

2006-07-14T14:14:00.000-04:00

Good news for cryonics:

WASHINGTON – The latest research on water - still one of the least understood of all liquids despite a century of intensive study – seems to support the possibility that cells, tissues and even the entire human body could be cryopreserved without formation of damaging ice crystals, according to University of Helsinki researcher Anatoli Bogdan, Ph.D.

He conducted the study, scheduled for the July 6 issue of the ACS Journal of Physical Chemistry B, one of 34 peer-review journals published by the American Chemical Society, the world's largest scientific society.

In medicine, cryopreservation involves preserving organs and tissues for transplantation or other uses. Only certain kinds of cells and tissues, including sperm and embryos, currently can be frozen and successfully rewarmed. A major problem hindering wider use of cryopreservation is formation of ice crystals, which damage cell structures.

cryopreservation may be most familiar, however, as the controversial idea that humans, stricken with incurable diseases, might be frozen and then revived years or decades later when cures are available.

Bogdan's experiments involved a form of water termed "glassy water," or low-density amorphous ice (LDA), which is produced by slowly supercooling diluted aqueous droplets. LDA melts into highly viscous water (HVW). Bogdan reports that HVW is not a new form of water, as some scientists believed.

"That HVW is not a new form of water (i.e., normal and glassy water are thermodynamically connected) may have some interesting practical implications in cryobiology, medicine, and cryonics." Bogdan said.

"It may seem fantastic, but the fact that in aqueous solution, [the] water component can be slowly supercooled to the glassy state and warmed back without the crystallization implies that, in principle, if the suitable cryoprotectant is created, cells in plants and living matter could withstand a large supercooling and survive," Bogdan explained. In present cryopreservation, the cells being preserved are often damaged due to freezing of water either on cooling or subsequent warming to room temperature.

"Damage of the cells occurs due to the extra-cellular and intra-cellular ice formation which leads to dehydration and separation into the ice and concentrated unfrozen solution. If we could, by slow cooling/warming, supercool and then warm the cells without the crystallization of water then the cells would be undamaged."

From cancer to nerve regrowth

2006-07-11T07:29:00.000-04:00

Cancer researchers at Columbia University Medical Center have found that a protein known for driving the growth of cancer also plays a surprising role in restoring the ability of neurons to regenerate, making it an important target for addressing spinal cord damage or neurological diseases like Alzheimer’s.

[...]

Dr. Iavarone added that there is no chance that such a therapy would cause cancer in the brain or spinal cord. “Neurons have completely lost the ability to create new cells so there’s no danger of creating a tumor. The only growth they’re capable of is regeneration of their axons,” he said.

I'm not a doctor (but I play one on TV), but from what I've heard that last statement is not completely true. A number of people have found that nerve cells can replenish themselves, albiet slowly. I don't think this would be much of a problem though.

Learning from progeria

2006-07-11T07:26:00.000-04:00

From EurekAlert!

PITTSBURGH--Carnegie Mellon University researchers Kris Noel Dahl and Mohammad F. Islam have made a new breakthrough for children suffering from an extremely rare disease that accelerates the aging process by about seven times the normal rate.

Dahl, an assistant professor of chemical and biomedical engineering at Carnegie Mellon, said her work with researchers at the National Cancer Institute of the National Institutes of Health (NIH), the John Hopkins University School of Medicine and the University of Pennsylvania reveals that children suffering from Hutchinson-Gilford Progeria Syndrome (HGPS) have an excessively stiff shell of proteins.

The nucleus in all three trillion cells of the human body contains the DNA genome, which is wrapped with a stiff protein shell called the nuclear lamina. Children with HGPS have a mutation in one of the proteins of the lamina shell. For years, experts have thought this mutation made their nuclei much softer and more likely to be ruptured when cells were under stress.

But in a Proceedings of the National Academy of Sciences (PNAS) Journal article to be published this month, Dahl and her colleagues show that the lamina shell in HGPS patients is stiffer than normal. However, stiffer isn't necessarily better. The stiffer lamina did protect the HGPS nucleus from some forces, but under excessive force the HGPS lamina was more brittle and eventually fractured.

"The mutant HGPS lamina is like an egg shell that cracks when excessive pressure or force is exerted against it," Dahl said. "By contrast, normal lamina resembles the rubbery outer shell of a racquetball, which does not break under stress or force but can assume its original shape even after hard play."

The researchers also think that the stiffer lamina in HGPS patients may be unable to communicate the proper biological signals to the DNA inside the nucleus to help the cell grow, which contributes to the disease.

Islam, an assistant professor of chemical engineering and materials science and engineering, says that the increased stiffness of the lamina may be caused by mutant proteins self-organizing into ordered structures within the HGPS lamina.

"This could make the lamina stiffer and cause fractures in the nuclei," Islam said. The healthy lamina remains disordered and therefore less rigid.

"Once we understand what causes the lamina to stiffen, we can try to reverse or stop the problem," Dahl said. "We think this stiffening mechanism happens over time with increased protein concentration, so we need to determine the tipping point that causes real problems."

When people grow old, the walls of the cell nuclei exhibit similar problems to the HGPS nuclei, like losing their round shape and perkiness. "Our NIH collaborators have also found that the normal aged nuclei show the same structural changes as HGPS," Dahl said.

###

Other experts involved in the research included Paola Scaffidi and Tom Misteli of the National Cancer Institute, Katherine Wilson from Johns Hopkins and Arjun Yodh from the University of Pennsylvania.

Calorie restriction

2006-07-07T12:37:00.000-04:00

May have just gotten easier. Something called "pinolenic acid" appears to cut calorie consumption by overweight people by 36%. Don't know if that applies to normal weight people, but hopefully it does. See the article on LEF here. Pinolenic acid is found in pine nuts, although it is not mentioned how many you have to eat to get the 3 grams of pinolenic acid from the study. I also notice that the 36% figure mentioned is “prospective food intake”. In a more recent study, this translated to about a 10% decrease in body weight for low calorie diet with pinolenic acid, and a 14% decrease for very low calorie.

CR in primates

2006-06-14T13:48:00.000-04:00

Diet, aging study gains $7.9 million grant
June 13, 2006
by Terry Devitt

[...]

At this point in the study, the disparities between the monkeys on a diet reduced in calories by 30 percent and those allowed to eat as much as they wish are clearly evident. "Most importantly, we're starting to see the separation of the survival curves," Weindruch says, noting that 90 percent of the animals who began the study on a reduced diet are still alive, while only 70 percent of the animals allowed to eat freely have survived to this stage.

[...]

The animals on a restricted diet exhibit 70 percent less body fat, and the fat tissue itself, Weindruch notes, is very different from the fat tissue in the control animals, those allowed to eat freely. His group has also observed that the animals that eat less have less insulin in their bloodstreams and less insulin resistance, which are opposite to increases seen in these hallmarks of type 2 diabetes.
"So far, we've had complete protection from type 2 diabetes," Weindruch explains. "Normally, 30 percent of the animals in a research colony will exhibit type 2 diabetes."

HealthFirst-Repairing humans

2006-06-02T10:44:00.000-04:00

By Leslie LoBue
(05/18/06)-- Over the years, we've heard miraculous stories about people getting artificial arms, legs, even hearts.
Some doctors say they can create artificial brains, or at least brain parts, that may help millions of people with diseases like Alzheimer's, Parkinson's, and epilepsy.
The future of the human race is about to take a turn.
"I think all human beings have wanted to be better than well. we have always wanted to transcend the limitations of the human condition," said James Hughes, the executive director of the World Transhumanist Association.
Hughes believes the world is headed for a superhuman future. "We have continued to invent new technologies to extend the reach of the human body. New tools and new ways of modifying the way the body works."
In Los Angeles, neuroscientist Theodore Berger has developed the first artificial brain part - a hippocampus to help people with Alzheimer's form new memories. "There's no reason why we can't think in terms of artificial brain parts in the same way we can think in terms of artificial eyes and artificial ears," Berger said.
Information would come into the brain the same way, but would be re-routed to a computer chip, bypassing the damaged area of the hippocampus. "What we're hoping to do is replace at least enough of that function, so there's a significant improvement in the quality of life."
The technology could also help stroke, epilepsy and Parkinson's patients.
At the medical college of Wisconsin, Doctor Jay Neitz is also on the super-human frontier. "Since we are human beings and we like to try new things, we could say 'Wow, wouldn't it be cool if we had a whole other dimension of vision?'"
Primates and humans have three photo-receptors and can see four basic colors - red, green, blue and yellow. Here's a newsflash: Birds, fish and reptiles have four photo-receptors.
"It is clear that it does allow them to see things that we cannot see. they must have this whole extra dimension of color that we miss out on."
Neitz is studying gene therapy to give humans that extra dimension. By injecting modified genes directly into the eyes of colorblind monkeys, he expects to change their world. "It's hard to imagine that you would even know what it would be like to have this extra dimension of vision," he said.
Neitz says we could see ultraviolet, infrared and all the new shades we'd get by combining them. "I personally, I like the idea of being able to make ourselves better."
"I think this is an intrinsic part of human nature, of the human condition that we see that we are limited. we live in a limited world, and we are trying to push beyond those limits," Hughes said.
Now, it's up to technology to see how far beyond those limits we can go.

Towards a "free radical theory of graying"

2006-06-02T10:41:00.000-04:00

Melanocyte apoptosis in the aging human hair follicle is an indicator of oxidative stress induced tissue damage
Petra Clara Arck, Rupert Overall, Katharina Spatz, Christiane Liezman, Bori Handjiski, Burghard F. Klapp, Mark A. Birch-Machin, and Eva Milena Johanne Peters

Oxidative stress is generated by a multitude of environmental and endogenous challenges such as radiation, inflammation, or psychoemotional stress. It also speeds the aging process. Graying is a prominent but little understood feature of aging. Intriguingly, the continuous melanin synthesis in the growing (anagen) hair follicle generates high oxidative stress. We therefore hypothesize that hair bulb melanocytes are especially susceptible to free radical-induced aging. To test this hypothesis, we subjected human scalp skin anagen hair follicles from graying individuals to macroscopic and immunohistomorphometric analysis and organ culture. We found evidence of melanocyte apoptosis and increased oxidative stress in the pigmentary unit of graying hair follicles. The "common" deletion, a marker mitochondrial DNA-deletion for accumulating oxidative stress damage, occurred most prominently in graying hair follicles. Cultured unpigmented hair follicles grew better than pigmented follicles of the same donors. Finally, cultured pigmented hair follicles exposed to exogenous oxidative stress (hydroquinone) showed increased melanocyte apoptosis in the hair bulb. We conclude that oxidative stress is high in hair follicle melanocytes and leads to their selective premature aging and apoptosis. The graying hair follicle, therefore, offers a unique model system to study oxidative stress and aging and to test antiaging therapeutics in their ability to slow down or even stop this process.--Arck, P. C., Overall, R., Spatz, K., Liezman, C., Handjiski, B., Klapp, B. F., Birch-Machin, M. A., Peters, E. M. J. Towards a "free radical theory of graying": melanocyte apoptosis in the aging human hair follicle is an indicator of oxidative stress induced tissue damage.

I think this could be a major breakthrough. If we can show that we can stop, or better yet reverse, the graying of hair, this would not only be a great show that aging in general can be controlled, but it would be a big money maker. Just think how many greying men out there would pay for such a treatment.

What stupidity is this

2006-05-31T07:59:00.000-04:00

http://www.longevitymeme.org/news/view_news_item.cfm?news_id=2432

I must say that I completely agree with Reason's thinking, who are these people to judge what we will be able to do with an extra hundred, or two, or more years to live? I for one won't get bored with living life. For those that do, they are free to choose to age and die, but let me make my own choice on how long I want to live.
"Leon Kass believes humanity risks striking a similar Faustian bargain if it pursues technology that extends life spans beyond what is natural. "
What exactly is a natural life span? Is that one where we live in caves, half starved, with no medicine and die at 25? Is that what these people are advocating? I really don't see the difference between pursuing the goals of further life extension and what we have already done to increase our life span. Penicillin may be considered natural as it came from a bread mold, but what about all the antibiotics derived from it that are constantly saving peoples lives? Should we forego their use? What about heart surgery, or organ transplants, or even blood transfusions? What about cholesterol lowering medications? Where do you draw the line?
"There is no research into extending the life span thousands of years," said Richard Miller, a pathologist at the University of Michigan. "That's fantasy."
Why not? Would that not be the natural extrapolation of where we are heading now? I think Mr. Miller is just trying to put off the debate, and it may be fantasy now, but it won't be for long.
It is not the knowledge that we will die by some certain age that spurs us to make the most of life, Hackler says, but the awareness that we can die at any moment—and that will not change even if we are immortal.
I think this hits the nail on the head, and I hate the way people misuse the term immortal. Immortal means without death, which we won't be, we would be ageless, which is completely different.
Determining how much ennui the average person can bear will be important if life extension ever becomes a reality, Hackler says, because extended boredom could result in prolonged unhappiness or higher incidences of suicide.
Why are people so clueless on this issue? If you get tired of living, just stop taking the meds, or if we finally eliminate the aging issue from ourselves internally, you can choose how you want to die. What is so wrong with that? Why do people see choosing to end ones own life as such a bad thing if one is competent to make that choice? Is it better to have that decision made for you?
"Even if you've seen everything, you might say 'Well, I want to go see India once again,'" he told LiveScience. "It seems there's a possibly never-ending cycle there."
If that's what someone chooses to do with their life, no matter how long it is, who has the right to deny them?
"The fact that there are still some countries that I've never been to does not ruin my life," Callahan said. "I've never been to Nepal or Antarctica but it's hard to work that up to some great tragedy of my life."
No, the great tragedy is that your life has to end at all, and until people see that as the tragedy it is, we'll be stuck right where we are right now.

Here's a link to the special report.

Heal thyself: Systems biology model reveals how cells avoid becoming cancerous

2006-05-18T15:18:00.000-04:00

A team of researchers used new biotechnology tools to discover an elaborate system of gene control that is triggered by damage to DNA. The model could aid the development of new therapeutic agents to combat a broad spectrum of diseases, including cancer, neurodegenerative diseases, and premature aging.

Read on...

Factor Isolated That Regenerates Nerve Fibers; Previously Unknown Molecule Spurs Regeneration in Optic Nerve

2006-05-16T14:49:00.000-04:00

Researchers at Children's Hospital Boston have discovered a naturally occurring growth factor that stimulates regeneration of injured nerve fibers (axons) in the central nervous system. Under normal conditions, most axons in the mature central nervous system (which consists of the brain, spinal cord and eye) cannot regrow after injury. The previously unrecognized growth factor, called oncomodulin, is described in the May 14 online edition of Nature Neuroscience.
[...]

UK extends gene screening of embryos

2006-05-10T14:09:00.000-04:00

They say this like it is a bad thing. I'm all for people having the choice to have their children not carry genetic risk factors. The ethics of this do, however, start down a slippery slope that we will have to contend with. I'm not one of those that hold the opinion that a fertilized egg is a human "entity". It has the potential to become one, but it is not one at that stage. There is a line that has to be drawn somewhere for when it is no longer "right" (or ethical, however you want to say it) for abortion to be an option, but 3 days is well on the other side of it than 6 months. I think people should be able to choose to have as much knowledge as we can give them about what their children will be like, and make a decision on their own whether that is something they want. I also think that people should be able to "design" traits into their children when that becomes an option in the not to distant future.
I think this may also be the only route for the human species to continue biological evolution, as we have such a large population that any good or bad traits get completely diluted by the huge population mixing, and the fact that we compensate for any negative defects that aren't fatal by correction/assistance with technology (i.e. glasses, hearing aids, wheelchairs, etc). How long would someone with 20/80 vision (what I had before LASIK) have survived without assistance 5000 years ago (not that long in evolutionary time)? Not long I would say. Certainly not long enough to produce offspring, and even if by some chance they did, how many could they support, not being able to see to hunt or gather food? Our current huge population and technological advancements are contributing to genetic stagnation of the species. I think the next evolutionary steps will be guided by our own hand, either biologically or "artificially".

15:20 10 May 2006
NewScientist.com news service
Gaia Vince
The genetic screening of embryos for a wider range of diseases, including breast, ovarian and colon cancers, has been approved by the UK’s fertility authority.
Until recently, the Human Fertilisation and Embryology Authority (HFEA) only permitted tests for diseases that cause severe disability or death in childhood and have a 100% certainty of being inherited, such as cystic fibrosis. A landmark ruling in November 2004 allowed embryos to be screened for an inherited gene that confers a high risk of bowel cancer in carriers during adulthood – in their 20s and 30s.
Now the HFEA has extended the licences it grants to 10 IVF clinics to allow them to screen a cell from a 3-day-old embryo for BRCA1 and BRCA2 genes, which carry an 80% risk of developing breast cancer; and the HNPCC gene, which is associated with an 80% risk of colon cancer.
BRCA1 also confers a 40% risk of ovarian cancer. These diseases usually do not affect people until they are in their 30s or 40s.
“Eugenic concepts"
Couples who carry the “susceptibility” genes will be able to use the test results to decide whether they want the embryo to be implanted. The move has led to criticism from disability and pro-life groups who fear that embryos will increasingly be selected according to “eugenic concepts of perfection”. They point out that disabled people often enjoy full and rewarding lives.
However, the HFEA argues that embryo selection regulations in the UK are tight and would not allow selection based on social factors. It also argues that cancers are serious and debilitating diseases and parents should be allowed to select the best health for their children.
The rules for pre-implantation genetic diagnosis of embryos vary around the world as each nation navigates its own path through the ethical debate.
In some countries, such as the US and India, embryos may be selected on the basis of gender, whereas other countries, such as Germany, have banned embryo screening for any purpose.

Spontaneous Regression of Advanced Cancer in Mice

2006-05-10T14:08:00.000-04:00

Summary of the Current Research

Introduction:

The diagnosis of cancer consumes a large percentage of many pathologists' time. The huge variety of types of tumors that occur in people requires complex analysis to plan correct treatment and to determine a patient's prognosis. Diagnostic testing enables pathologists to learn how large a primary tumor has grown, how extensively it has spread and — most importantly — exactly what type of cancer it is.

When they think of cancer, most people assume that these various tumor types, once they occur, are inexorable in their progression unless they are successfully stopped by treatment. Pathologists often think the same way, in large part because the examples we see most often are in those patients in whom cancer has progressed to a size sufficient to be detected.

Occasional inklings from earlier laboratory studies, however, and some rare patient reports, suggest that cancer sometimes spontaneously disappears without treatment. Because such cases are extremely rare, and essentially impossible to study, many scientists have dismissed the phenomenon of "spontaneous regression" of cancer as either a mistaken diagnosis or fiction. Yet, such cases have actually been carefully documented in the past, and they certainly do happen.

Do these reports suggest that cancer cells really do not grow "in a vacuum," but are affected by control mechanisms that already exist in the body? Does cancer reach a detectable size because these controls have failed? If so, could such controls be identified, and enhanced in patients to provide new therapies? In fact, how do cancer cells actually “succeed” in patients? Do they actively inhibit protective processes that ordinarily would prevent cancer? Do cancers occur continuously during our lifetimes, yet are eliminated by internal mechanisms so that they are never seen?

The answers to such questions are the stuff of speculation, but a newly discovered mouse at Wake Forest University has shown that some of these ideas may not be so far-fetched.

Continue Reading:

New technology enables faster, more efficient cell harvest: Cell therapy meeting study

2006-05-04T13:29:00.000-04:00

East Hills, NY - - A new, transformative filtration-based technology for the isolation and enrichment of cells, a critical first step in the development of therapies to repair or replace diseased or damaged tissues and organs, was found to be more efficient and faster than traditional technology used for cell separation. These findings were presented today at the International Society for Cellular Therapy (ISCT) annual meeting in Berlin, Germany. The Pall Corporation (NYSE: PLL) Filter Harvest System was found to have the potential to become a valuable tool to help realize the promise of regenerative medicine, a field that scientists believe could produce significant breakthroughs in the treatment of heart disease, cancer, diabetes, bone injury and many other acute and chronic conditions.
Lisa Bradbury, Ph.D., Director, R&D Cell Therapy, Pall Life Sciences, presented data comparing the Pall Filter Harvest System to a traditional open-system, density gradient, centrifuge-based method for isolation of mononuclear cells (MNC) from whole blood. The Pall Filter Harvest System was found to significantly reduce processing time; it can be performed in less than 15 minutes compared to an average processing time of about 2.5 to 4 hours with the Ficoll gradient technique. The Filter Harvest System also exhibited higher yield of MNCs for significantly better recovery (60 to 95 percent) than the Ficoll method.
The Pall Filter Harvest system can be used as a closed system that adheres to Good Manufacturing Practice (cGMP), furthering the ability to comply with increasingly stringent regulations for safe, reproducible and efficacious cell products. In addition to rapid processing, the Pall system can be performed at point of use (operating room). It does not require the addition of laboratory equipment or trained technicians, as the method is easy to learn and use.
"Researchers and companies working in cell therapy expressed the need to find better and easier ways to isolate and enrich cells that result in higher cell yield, faster processing time, ease of use and are also more likely to meet future regulatory requirements," stated Judy Angelbeck, Ph.D., Senior Vice President, Pall New Technologies. "Pall was able to translate its material science expertise on the interactions between media and cells based on our long-standing leadership in blood filtration to develop this new approach to cell harvesting."
The Pall system can be used to harvest cells from a broad range of biological samples including peripheral blood, bone marrow and umbilical cord blood. The Company is currently working with several companies in applying its filter harvest system to the development of innovative cell-based therapies in a variety of therapeutic areas, including orthopedics.
"We are pleased that Pall technology can play a key role in the revolutionary advances now occurring in medicine by providing researchers with the tools to take novel cell therapies from the laboratory into the clinic, as part of our goal to make cell therapy safe, routine and simple," Dr. Angelbeck added.
Regenerative medicine, which includes cell therapy, is a promising area of scientific research with application in the treatment and cure of a rapidly expanding list of diseases and injuries. Scientists believe cell-based therapies could be used to repair damaged heart muscle following a heart attack, replace skin for burn victims, restore movement after a spinal cord injury and regenerate pancreatic tissue to produce insulin for people with diabetes. Regenerative medicine promises to improve health and quality of life by supporting and activating the body's natural healing abilities.

Original Article

Wrinkled cell nuclei may make us age

2006-04-28T10:13:00.000-04:00

Blocking a aberrant protein could keep cells pert and young.
Helen Pearson

In the continued quest to pinpoint the molecules that turn us wrinkly and grey, some scientists are beginning to think that the walls of the cell nucleus might play an important role.

A new study shows that cells from people over the age of 80 tend to have specific problems with the nucleus that young children's cells do not. The elderly nucleus loses its pert, rounded shape and becomes warped and wrinkled.

The discovery supports the up and coming idea that at least part of the normal ageing process may be driven by the nucleus' decay, and that blocking this might curb some of time's toll upon the body. "If this really has a physiological role in normal elderly people then it's a huge deal," says David Sinclair who studies the molecular mechanisms of ageing at Harvard Medical School, Cambridge, Massachusetts.

Old before our time

Researchers have found many different genes that can alter the lifespan of animals. In addition, some environmental factors, from the amount of food we eat to the number of cigarettes we smoke, are thought to contribute to the speed at which we age. But there is no consensus yet on how, exactly, these things combine to make our cells and bodies start to fail.

One widely held idea is that cells accumulate wear and tear over a lifetime from damaging molecules known as reactive oxygen species. Some researchers have focused on problems with the power-generating components of cells, called mitochondria. And others have looked at how the ends of chromosomes, called telomeres, fray as we get older.

To gain insight into human ageing, in recent years some biologists have focused their attention on a group of diseases known as progerias, in which children can suffer baldness, heart disease and other symptoms of premature ageing.

In 2003, scientists showed that one such rare disorder, called Hutchinson-Gilford progeria syndrome (HGPS), is caused by a mutation that affects the lamin A protein, a building block of the nucleus and its wall. Now Tom Misteli and Paola Scaffidi at the National Cancer Institute in Bethesda, Maryland, have shown that elderly people tend to have the same problem with their cell nuclei, suggesting that this protein is important in the normal ageing process.

Turning back the clock

In cells taken from the elderly, the nuclei tend to be wrinkled up, the DNA accumulates damage, and the levels of some proteins that package up DNA go askew, the team reports in Science¹. This mirrors the same changes that they previously observed in cells from HGPS children.

The team suggests that healthy cells always make a trace amount of an aberrant form of lamin A protein, but that young cells can sense and eliminate it. Elderly cells, it seems, cannot.

Critically, blocking production of this deviant protein corrected all the problems with the nucleus. "You can take these old cells and make them young again," Misteli says.

This suggests that drugs that do the same thing might slow or stay some symptoms of ageing. This is the next key experiment that needs to be tried in animals, researchers say.

Cancer cells suppress large regions of DNA by a reversible process that can be tackled

2006-04-25T14:35:00.000-04:00

Cancer researchers at Sydney's Garvan Institute, in collaboration with Spanish scientists, have formulated a new concept for how cancer cells can escape normal growth controls, which may have far-reaching implications for the new generation of cancer therapies.
They have found large regions of DNA are 'switched off' in colon cancer. Lead researcher Associate Professor Sue Clark, of the Garvan Institute, says: "These large regions – referred to as suburbs – contain genes that normally function to prevent the development of tumours".
Our cells become cancerous when the normal controls over cell growth and death go awry. This deregulation has traditionally been linked to DNA mutations of single genes or deletion of large sections of the chromosome. However more recently it has become clear that gene silencing in cancer can also occur, in the absence of changes to the DNA sequence: a phenomenon known as 'epigenetics'. DNA methylation is one of the main epigenetic processes.
In cancer, the DNA methylation pattern of many genes changes. However, until now, it was believed that only individual single genes were silenced by methylation. But this is not necessarily the case. "What we've found is that non-methylated genes that reside in a particular suburb near methylated genes are also silenced. Their physical proximity to the methylated genes affects their ability to function. It's a case of being in the wrong neighbourhood at the wrong time", says Assoc. Professor Clark.
The Garvan team developed a new method to scan the entire complement of the 30 000 plus genes – the entire genome – in the cancer tissue samples, which allowed widespread changes to be identified in specific parts of the genome.
They were amazed to find the extent of gene silencing. Assoc. Professor Clark adds: "What we want to do now is determine if these same regions are switched off in other types of cancers".
The team also hope that new cancer therapies, which can reverse DNA methylation, will restore the cell's normal regulation and treat and prevent cancer.

Drumming up better hearing

2006-04-25T14:17:00.000-04:00

Scientists at the Lions Ear and Hearing Institute in Nedlands are closer to growing artificial eardrums to replace those damaged by explosions, trauma and infection.
Already they have been the first in the world to successfully harvest and grow eardrum cells - called keratinocytes - in a test tube.
Now a team led by institute molecular geneticist Reza Ghassemifar will take the next step towards completing the tissue engineering process.
Over the next three years they hope to recreate the best biological chemical conditions so the cells grow into a sheet of eardrum that can be transplanted.
"In the next five years we hope to be able to replace a hole in an eardrum with a functional, artificial eardrum," Dr Ghassemifar said.
This would be done by taking a small piece of a patient's own damaged eardrum tissue - to reduce chances of later rejection - and from it growing new cells on a mesh in the laboratory, he said.
Within a few weeks, the new tissue could be given to a surgeon who could use it to patch the hole.
But first, the challenge was to stimulate the harvested cells to grow into the appropriate structure, outside the body.
"Every eardrum is a very thin, translucent, three-layered membrane around 10 microns thick," Dr Ghassemifar said.
"Using a particular chemical mix - which remains closely guarded - we are trying to stimulate the cells to grow and differentiate into the three layers similar to normal eardrums."
Gene therapy will be used to keep the harvested cells alive and improve their ability to "sit tightly" and adhere to their supporting mesh, he said.
Before being trialled in humans, the engineered eardrums will be tested in animals.
The work will be funded by a $240,000 grant from the Garnett Passe and Rodney William Memorial Foundation, which is dedicated to funding leading-edge research in the areas of ear, nose and throat surgery.
-Alison Batcheler

Solar-powered retinal implant

2006-04-20T12:41:00.000-04:00

AN IMPLANT that squirts chemicals into the back of your eye may not sound like much fun. But a solar-powered chip that stimulates retinal cells by spraying them with neurotransmitters could restore sight to blind people.
Unlike other implants under development that apply an electric charge directly to retinal cells, the device does not cause the cells to heat up. It also uses very little power, so it does not need external batteries.
The retina, which lines the back and sides of the eyeball, contains photoreceptor cells that release signalling chemicals called neurotransmitters in response to light. The neurotransmitters pass into nerve cells on top of the photoreceptors, from where the signals are relayed to the brain via a series of electrical and chemical reactions. In people with retinal diseases such as age-related macular degeneration and retinitis pigmentosa, the photoreceptors become damaged, ultimately causing blindness.
Last year engineer Laxman Saggere of the University of Illinois at Chicago unveiled plans for an implant that would replace these damaged photoreceptors with a set of neurotransmitter pumps that respond to light. Now he has built a crucial component: a solar-powered actuator that flexes in response to the very low intensity light that strikes the retina. Multiple actuators on a single chip pick up the details of the image focused on the retina, allowing some "pixels" to be passed on to the brain.
The prototype actuator consists of a flexible silicon disc just 1.5 millimetres in diameter and 15 micrometres thick. When light hits a silicon solar cell next to the disc it produces a voltage. The solar cell is connected to a layer of piezoelectric material called lead zirconate titanate (PZT), which changes shape in response to the voltage, pushing down on the silicon disc. In future, a reservoir will sit underneath the disc, and this action will squeeze the neurotransmitters out onto retinal cells.

From here we just need to be able to generate the neurotransmitter in the device.

Nanospheres: complete prostrate tumor elimination

2006-04-19T07:05:00.000-04:00

An MIT/Harvard collaboration on treating prostate cancer in mice just published in PNAS:
“A single treatment of drug-bearing nanoparticles effectively destroys prostate cancer tumors in mice, according to experiments by researchers at MIT and Harvard Medical School. This approach could lead to powerful treatments without the side effects associated with cancer therapy, say the scientists.
” ‘We did a single injection of the particles, and then followed the tumor for the next 109 days, and showed that we basically had complete tumor elimination,’ says Omid Farokhzad, assistant professor of anesthesia at Harvard Medical School, who, along with Robert Langer, chemical engineering professor at MIT, led the research. Because the ingredients used to make the nanoparticle drug system have already been okayed by the FDA for other purposes, the researchers hope to win quick approval for testing the new technology in humans…
“The MIT-Harvard researchers are also working on targeting pancreatic cancer and eventually breast cancer and cardiovascular disease…
“Eventually, the MIT-Harvard researchers hope to design nanoparticles that can be injected into the bloodstream, from which they could seek out cancer cells anywhere in the body, making it possible to treat late-stage metastasized cancer.”
“Early toxicity trials of the nanoparticles could begin in two years, if further animal studies go well…”

Regrow Your Own

2006-04-11T10:51:00.000-04:00

April 11, 2006
By NICHOLAS WADE
Stem cell therapy has long captured the limelight as a way to the goal of regenerative medicine, that of repairing the body with its own natural systems. But a few scientists, working in a relatively obscure field, believe another path to regenerative medicine may be as likely to succeed. The less illustrious approach is promising, in their view, because it is the solution that nature itself has developed for repairing damaged limbs or organs in a wide variety of animals.
Many species, notably amphibians and certain fish, can regenerate a wide variety of their body parts. The salamander can regenerate its limbs, its tail, its upper and lower jaws, the lens and the retina of its eye, and its intestine. The zebra fish will regrow fins, scales, spinal cord and part of its heart.
Mammals, too, can renew damaged parts of their body. All can regenerate the liver. Deer regrow their antlers, some at the rate of 2 centimeters a day, said to be the fastest rate of organ growth in animals. In many of these cases, regeneration begins when the mature cells at the site of a wound start to revert to an immature state. The clump of immature cells, known as a blastema, then regrows the missing part, perhaps by tapping into the embryogenesis program that first formed the animal.
Initiation of a blastema and the formation of the embryo are obviously separate biological programs, but "the processes must converge at some point," says Jeremy Brockes, a leading regeneration researcher at University College London.
The blastema seems to derive its instructions from the wound-site cells from which it was formed, and is quite impervious to cues from new surrounding tissue if it is transplanted. If a blastema made by sectioning a salamander's limb at the wrist is transplanted elsewhere in the body it will still grow just a wrist and paw, while a shoulder blastema will regrow the whole limb. People, of course, cannot regrow their limbs like newts, and do not form blastemas, so the relevance of regeneration to medicine has long seemed remote. But the capacity for regeneration exists in such a wide variety of species that it is unlikely to have evolved independently in each, regeneration researchers believe.
Rather, they say, the machinery for regeneration must be a basic part of animal genetic equipment, but the genes have for some reason fallen into disuse in many species.
In support of this notion, people are not wholly lacking in regenerative powers.
There are reports that the tip of the finger can occasionally be regenerated, if the cut is above the last joint. And people can vigorously repair damage to the liver. Even after 75 percent has been removed in surgery, the liver regains its original mass in two to three weeks. It is not certain why other organs and limbs have lost this useful capacity, but perhaps only the liver was damaged often enough during its owner's lifetime to make a repair system worth the cost. "I believe that the reason is the extensive and recurring injury that the liver was exposed to in evolution: rotten food, plant toxins, viruses," says Markus Grompe, a liver expert at the Oregon Health and Science University.
The liver can regenerate itself, when all else fails, from stem cells, the versatile cells that produce the mature cells of many organs and tissues. But usually it relies on its own mature cells, which, like those of a blastema, possess a remarkable power to divide and multiply, even though they can only restore the organ's mass, not its original structure.
A more specific reason for thinking regeneration is not a wholly lost ability comes from genes. Last December, Mark Keating, who studies regeneration in zebra fish, identified a gene that is essential for initiating blastema formation when the fish's fin is cut. Both this gene, called fgf20, and another he has found, hsp60, also exist in people, suggesting the genetic basis for regeneration may still be in place even though the body can no longer evoke it.
Dr. Keating, a vice president at the Novartis Institutes for Biomedical Research in Cambridge, Mass., believes stem cells can ordinarily undertake only very limited repairs of organs like the liver and heart, and that the scarring often seen in these tissues is a fallback mechanism put in place when the stem cells' capacities are exceeded.
If the genes that boot up the zebra fish blastema also exist in people but are not switched on, perhaps some drug might be developed that goads them into action. Once a blastema had been induced at some wound site in the body, regeneration researchers suggest, it might regrow the missing limb or organ with no further intervention required. "Maybe there are residual abilities that could be enhanced" in mammals, says Shannon Odelberg, a researcher at the University of Utah. He studies regeneration in the newt, with the eventual goal of inducing blastemas to form in mammals.
Regeneration is studied in only a few laboratories. It was not even on the agenda of the research planning meeting held last October by the California Institute of Regenerative Medicine, which was dominated by stem cell biologists.
One reason for this orphan status is that the model animals used by most biologists, like the roundworm, the fruitfly and the mouse, happen to be ones that do not regenerate.
The genetics of regenerating animals, like the salamander, are largely unknown. Hence the process of regeneration has received little attention from research biologists. But there is a group of vertebrates that can regenerate very successfully, said Dr. Brockes. "It would be rather surprising if there weren't some interesting and important lessons one could learn from them."
"Regeneration is the result of an evolutionary experiment that nature has already done for us," said Alejandro Sánchez Alvarado, a Hughes Institute researcher who studies flatworm regeneration at the University of Utah The blastema, he notes, performs the difficult task — one not faced by the embryo — of integrating new and existing tissues.
Many proponents of regeneration, while conceding they have a great deal more to learn, believe stem cell therapy too may not be as close to clinical use as its advocates sometimes suggest. Dr. Brockes noted that the blastema's reliance on internal information contrasts with a principal assumption of stem cell therapy, that stem cells inserted into a damaged tissue will use local cues to behave appropriately and integrate into the surrounding tissue.
Stem cell therapists assume that injected cells can replace missing tissue with guidance from the invisible template supplied by chemical signals from nearby cells. That is the solution a human engineer might logically think of, Dr. Brockes said, but evolution has chosen a different one.
The basic biology of regeneration is not yet fully understood, but nor is that of stem cells. Indeed, it may be premature to start thinking about how to use stem cells therapeutically, said Dr. Sánchez Alvarado.
"Translating a biological process you don't understand into technology is like trying to translate hieroglyphs without a Rosetta Stone," he said.
Dr. Grompe, the expert on liver regeneration, said that getting stem cells to behave properly in a patient's body "is a very, very difficult problem." With transplanted stem cells, the usual outcome is "nonfunctional at best and cancerous at the worst because the local environment is not able to modulate the behavior," he said. "I think that cell therapy of the nervous system will be extremely difficult because of that. So much for stem cells curing Alzheimer's."
Dr. Keating believes that the expense of stem cell therapy, should it work, is a major consideration. "I would never begin to guess that the whole stem cell approach has no chance of working," he said. But even if it does, developing cells for every patient who needs them would be very expensive. Switching on the regenerative process with drugs, should that prove possible, would be cheap by comparison, he said.
Scientists who work on stem cells reject the idea that the blastema mechanism is the only way to repair the body's tissues. "I agree that blastema regeneration models might have something to tell us, but I wouldn't give up on normal stem cell regeneration," said Irving Weissman, a leading expert on blood stem cells at Stanford University. The stem cells involved in bone marrow transplants "can regenerate drastic loss of tissue," he said.
Bone marrow transplantation is the big success story on which much of the hope for stem cell therapy is based. But regeneration researchers believe the bone-marrow example may be misleading because blood is not an organized tissue, and the marrow's blood-making stem cells are not required to do anything much beyond their usual function.
In disagreement with this view, Dr. Weissman said that blood-making stem cells are highly versatile and have the ability to home in on the marrow and set up shop in their proper niche there, and that neural stem cells appear to have a similar degree of versatility. Human neural stem cells, when put into embryonic mice, will migrate through the mouse's brain and add insulation to mouse neurons that lack it.
Robert Weinberg, a biologist at the Whitehead Institute in Cambridge, said therapeutic regeneration was "decades away" because the cells of animals that regenerate are so different from those of people.
But there is great hope of taking embryonic stem cells, he said, and making them yield primitive adult stem cells that still possess regenerative capability. He placed less confidence in using fully mature adult stem cells, which may have lost the ability to build new tissue. "I think the notion of trying to extract adult stem cells from adult tissues is possibly a fool's errand," he said.
In the light of new knowledge, some stem cell biologists are making more guarded predictions about the imminence of stem cell therapy. Ron McKay, an expert on neural stem cells at the National Institutes of Health, noted that stem cells inserted into the developing brain of a fetal animal "become incorporated in an extraordinary way, as if local cues were controlling their behavior."
But in the adult brain, he said, nothing happens, suggesting that the concept of using stem cells to treat Alzheimer's disease is illusory.
Stem cells head the hierarchy of cells with which nature organizes animal tissues, but so much remains to be understood that it is hard to tell which aspect of their biology may hold therapeutic promise. "I think the idea of cell therapy per se will not be that powerful a tool for most diseases," Dr. McKay said. "But stem cell biology will be a hugely important tool."
Regeneration and stem cell therapy are promising aspects of regenerative medicine but both are still at the research stage. "I'm very bullish on regenerative medicine," said Dr. Keating, alluding to both types. "I think it's going to happen and it will be a revolution, but it will take time. It would be a mistake to oversell it and promise too much too early."

Mayo Clinic Researchers Challenge Sepsis Theory

2006-04-10T14:39:00.000-04:00

Propose new approach for better treatment of deadly condition
A Mayo Clinic research team has challenged the accepted theory on the cause of sepsis -- a condition in which the body's cells generate fever, shock and often death. Sepsis is thought to occur when poisons from bacterial infection interfere with the cells. The Mayo researchers challenge that long-held concept with a new theory in an opinion piece in the current issue of Trends in Molecular Medicine http://www.sciencedirect.com/science/journal/14714914. Their findings suggest that sepsis begins with a change in certain cellular receptors that then provoke widespread inflammation, even in the absence of bacteria or their poisons.
"We think people have been focusing too exclusively on a single causal factor of sepsis for the last 150 years and, as a result, therapeutically aiming at the wrong target -- the bacteria and the poisons they produce," says senior author Jeffrey Platt, M.D. "That's why the death rate remains so high despite efforts to block the poisons."
The researchers define a new "first step" that initiates the sepsis syndrome cycle. In this step, a critical receptor for bacterial poisons and for some of the body's own substances is liberated from "natural suppression." Once free to function, the receptor can trigger the catastrophic cascade of events that is sepsis. The sepsis syndrome can occur during a bacterial infection, as the accepted medical principle holds, or -- as the Mayo Clinic team theory suggests -- it also can occur when substances the body makes act like the bacterial poisons. The Mayo investigators suggest that some or even many cases of sepsis may actually be caused by these normal body substances. The Mayo team argues that this new understanding of how sepsis arises could lead to new treatments for this major medical problem.
Significance of the Mayo Clinic Research
Approximately 700,000 cases of sepsis occur annually in the United States, half of which are fatal. Sepsis is the second most common cause for admissions to critical care units and can be a significant complication of some heart surgeries. The Mayo Clinic researchers believe current sepsis treatment isn't more effective because the theory of sepsis is too narrow. Current treatments don't target all causes of sepsis syndrome -- only the bacterial poison cause -- which was described by a 19th century researcher as "the putrid gift."
"Our work is the first to show that this change in receptors in the body is the first true step in the sepsis syndrome, rather than the introduction of a poison," explains Dr. Platt. "The importance then becomes clear. If we really do now have the first cause of sepsis -- not the bacteria, but the unconstrained receptors -- then we can therapeutically interfere with that receptor release mechanism by designing new treatments and possibly, and at long last, develop drugs that treat all cases of sepsis."
Challenging Existing Theories
Dr. Platt and his colleague, Gregory Brunn, Ph.D., say the evidence they've published compels this conceptual shift about sepsis. "The problem with the concept of sepsis, and what provoked some of our interest, is that it has been known for 10 years that when you treat with anything that interrupts bacterial poisons, it has no impact on the septic disease. That suggests that perhaps the poisons don't cause sepsis after all," Dr. Platt says. "Problems such as this caused us to ask, 'Could there be something else driving sepsis, other than the classic poisoning explanation?'"
Mayo Discovers Key Piece of the Puzzle
Dr. Platt and colleagues discovered several years ago that certain naturally-occurring molecules can stimulate receptors once thought to be exclusive for the bacterial poisons (endotoxins). Once stimulated, the receptors (toll-like receptors) set the sepsis cycle into motion. "This finding was very exciting," notes Dr. Platt. "It explained how the sepsis syndrome can occur when there isn't an infection -- which it does in some cases."
However, Drs. Brunn and Platt saw an obvious problem with this explanation. If normal substances from the body can stimulate toll-like receptors and cause the sepsis syndrome, why aren't we all desperately ill with sepsis? Dr. Brunn explains, "Our bodies are not poised to respond to sepsis. Our bodies are held in check by the fact that this molecule-receptor system is constrained in its activity. What causes sepsis -- and the syndrome like sepsis that can happen in cancer or trauma or in response to drugs -- is that this receptor gets released from its constraint. That's the first step that actually initiates sepsis." Research is underway to discover new therapies that could prevent, blunt or reverse the release of the constrained receptor.

For the first time: Longevity modulated without disrupting life-sustaining function

2006-04-10T14:14:00.000-04:00

"The central question [is] whether we would be able to genetically manipulate one element of the pathway without disrupting its additional functions," said Dillin. "In this regard, we thought that the life extending function of this pathway would be elusive, whereas the developmental and reproductive functions would be more amenable. We were delighted to find that Smk-1 proved to be specific for the one function we thought the most elusive," he added.
Some of Dillin's earlier research had hinted at the possibility that "specificity" factors may control how and whether insulin and IGF-1 impact a target gene. Identifying those factors one by one would allow scientists to separate the different functions of insulin/IGF-1 signaling and to manipulate them individually without wreaking havoc on the organism's normal functioning.
Together with the lab of another Salk scientist, Tony Hunter, Ph.D., Dillin's team identified a protein in the worm Caenorhabditis elegans that allowed them to do just that. The protein is encoded by the Smk-1 gene. "Smk-1 is the first known gene that regulates longevity without affecting other vital functions of the insulin signaling pathway," said Wolff.
Under favorable conditions, a still unidentified molecule binds to DAF-2, the worms' equivalent of the insulin/IGF-1 receptor, which is located at the cell's surface. A cascade of signaling molecules relays the information deep into the cell till it reaches a protein called DAF-16. Known as a transcription factor, DAF-16 encodes a DNA-binding protein that turns on other genes but when DAF-2 is active, it is unable to enter the cell's nucleus to activate its target genes.
When environmental conditions turn harsh as a result of overcrowding and scarce nutrients, for example, DAF-2 signaling shuts down. No longer marooned outside the nucleus, DAF-16 crosses into the nucleus, and triggers all the necessary genes to help the body take care of the stressful situation. But food shortages aren't the only triggers for the stress program. Others are the heat that scrambles proteins into toxic clumps and marauding parasites. Highly reactive molecules known as free radicals also unleash DAF-16.
If the worms are having a good day in a favorable environment, but for some reason DAF-2 signaling gets turned off precociously, the worms reap the benefit of increased stress resistance and double their lifespan from an average of 20 to 40 days. Except the worms trade a trim life focused on reproduction for a long life with fewer progeny and a tendency to halt larval development and enter a dormant, hibernation-like stage in which they can hang on for months but don't reproduce.

Original article here.

Altering genetic blueprint of receptors in brain could help stroke victims avoid brain damage

2006-04-10T13:10:00.000-04:00

A University of Central Florida researcher has demonstrated that altering AMPA receptors in animals improved their chances of surviving strokes and remaining healthier afterwards.
A University of Central Florida researcher has discovered that altering a receptor that mediates communication between nerve cells in the brain significantly improves animals' chances of surviving strokes and allows them to remain healthier afterwards.
YouMing Lu, a professor at the UCF Burnett College of Biomedical Sciences, is hopeful that changing the genetic blueprint of AMPA receptors can help to block lethal flows of calcium into neurons of human stroke victims.
If administered within a few hours of cardiac arrest, such therapies could prevent brain damage. Given later, the therapies could speed up the regeneration of neurons to replace ones killed by the stroke. In both cases, the primary goal is to help patients avoid brain injuries after strokes.
AMPA receptors that are located at the surface of nerve cells are normally responsible for learning and memory formation. During strokes, however, the receptors become toxic to nerve cells.
"We're trying to find out what the major toxic aspects of these receptors are so we can rescue neurons without damaging learning and memory formation," Lu said.
Lu's research was published in the March 2 issue of Neuron, a prestigious biomedical research journal. Lu and his research team at UCF and the University of Calgary are trying to determine the molecular functions that lead to receptors opening up and enabling large, lethal flows of calcium to reach neurons after strokes.
The calcium flows occur in the hippocampus of the brain, an area that is critical for learning and memory processes. The dilemma for researchers is to figure out how to protect neurons from the lethal doses of calcium without causing more damage to learning and memory.
Lu's approach of modifying one part of the genetic blueprint of the AMPA receptor protected the brain in tests with mice and rats, which experience the same pattern of brain damage after cardiac arrest as humans do, Lu said. More tests in animals would be done before clinical trials are conducted.

Originial article here.

AGE Crosslink breaker

2006-04-06T12:22:00.000-04:00

I don't know how many people know about this product, but it is currently only under trials for heart conditions and erectile disfunction. Seems to me it has a good fit in Aubrey's SENS plan. I'd like to see someone do testing with it to see if it helps longevity in mice.

Alagebrium is the only A.G.E. Crosslink Breaker in advanced human testing. The compound has demonstrated promising results in several Phase 2 human clinical trials and is being developed initially for cardiovascular and vascular diseases. Results to date suggest that alagebrium may be a novel therapy for a number of conditions that occur as a result of myocardial or vascular alterations associated with aging or diabetes. Preliminary evidence suggests that the compound is able to modify both the structure and function of the left ventricle (main pumping chamber of the heart) consistent with a partial reversal of pathology. Similarly, alagebrium has been shown to improve the reactivity and function of the arterial system. In addition, in all clinical testing to date, the compound has demonstrated a clean safety profile.

Some validation for CR in humans

2006-04-05T12:49:00.000-04:00

Cutting calories may boost your lifespan
NewScientist.com news service
Roxanne Khamsi
People who substantially cut their calorie intake develop some of the traits associated with longevity discovered in animal tests, a new study reveals.
Cutting calories reduced body temperature and levels of the metabolism hormone insulin, as well as decreasing DNA damage, showed the study. But follow-up tests are necessary to find out if these biological effects, which occurred relatively quickly, last for more than a few months.
Scientists hoping to understand the biological mechanisms that control ageing have increasingly given attention to the idea that reducing food intake can extend life.
Studies in rodents and other lower species have shown that long-term calorie restriction can boost longevity – increasing the maximum lifespan of mice and rats by about 30% and protecting them against blood vessel plaques and cancer. But with less experimental data from humans, researchers remain undecided about what to recommend to people.
Eric Ravussin of Louisiana State University in Baton Rouge, US, and colleagues conducted a trial with 48 volunteers randomly assigned to maintain their weight or reduce their calorie intake.
Calorie burning
Twelve of the people recruited for the trial ate enough food to maintain their weight. Of the remaining 36 people, an equal number were assigned to either cut their calorie intake by 25%, cut their calorie intake by 12.5% and burn 12.5% more calories with exercise, or to follow a stringent diet of just 890 Calories a day (until they lost 15% of their start weight, followed by a weight maintenance diet).
Participants received their prescribed meals at the research centre for the first three months of the experiment. The volunteers also attended weekly group meetings and had mid-week telephone calls to help them stick to their diets.
People on the caloric restriction diets lost an average of 10% or more of their weight. The researchers also found that these subjects had reduced fasting levels of the hormone insulin, a trait associated with longevity in animal research.
They also found that volunteers who restricted their caloric intake by 25% or achieved similar results by cutting calories and upping exercise had a reduced average core body temperature at the conclusion of the six month trial. Lower body temperatures are also associated with longevity.
Each of the low calorie groups also showed a small but statistically significant reduction in DNA damage in their blood cells, when compared with the control individuals. This is noteworthy, the researchers say, because some of the chemical by-products of food metabolism attack DNA, which might contribute to cancer and accelerate the effects of ageing.
Journal reference: Journal of the American Medical Association (vol 295, p1539)

Bio-engineered bladders successful in patients

2006-04-04T08:36:00.000-04:00

NewScientist.com news service
Roxanne Khamsi
Bladders engineered in the laboratory from patients' own cells and then implanted into the body have succeeded in their first clinical trial.
The feat was accomplished by Anthony Atala, at Wake Forest University Medical School in Winston-Salem, North Carolina, and his colleagues. He says that while scientists have had success with skin transplants grown on scaffolds in the past, this is the first time they have grown and transplanted a discrete, complex organ.
The success is the culmination of an idea that the team began exploring 16 years ago. Atala adds that they are also working on growing bio-engineered hearts and pancreases in the lab. Growing organs from a patient's own cells means the organs are not rejected after transplantation.
To create the new bladders, the researchers took a biopsy from patients whose bladders functioned poorly due to an inherited nervous system disorder. The team then placed muscle cells and cells from the bladder lining on a biodegradable bladder-shaped scaffold and allowed them to grow for about two months.
The scaffolds were made of the structural protein collagen, in some cases adding polyglycolic acid, a polymer used in surgical sutures.
Major milestone
The team then transplanted these new bladders into their patients in a delicate operation and monitored their recovery. Two of the patients did not provide follow-up information. But Atala’s group did track the progress of seven patients, aged between 4 and 19 years, for an average of nearly four years.
The patients with the bio-engineered bladders gained better urinary control. The improvements were similar to those resulting from standard surgery that relies on intestinal grafts to fix the bladder. But the new technique does not require any damage to the intestine, the researchers note.
“Atala and his colleagues should be praised for the milestone they have reached, but further multi-institutional studies are needed with longer follow-up,” writes Steve Chung, of the Advanced Urology Institute of Illinois in Spring Valley, Illinois, in a commentary on the study appearing in the Lancet. Until then, he adds, surgery using intestinal tissue to repair the bladder “remains the gold standard”.
Bladder disease does not only cause urinary control problems but can lead to kidney damage. At present, reconstructive surgery is often performed to treat severe bladder problems.
This procedure involves grafting tissue from a section of the small intestine or stomach. But medical experts say that many complications can arise from this type of procedure.
Journal reference: Lancet (DOI: 10.1016/S0140-673(06)68438-9)

First clinical trial of gene therapy for muscular dystrophy now under way

2006-03-30T10:21:00.000-05:00

The first gene therapy human trial in the United States for a form of muscular dystrophy is under way.
The clinical trial for Duchenne muscular dystrophy (DMD) tests the safety and effectiveness of a therapy that was developed over two decades by scientists at the University of North Carolina at Chapel Hill's School of Medicine and the University of Pittsburgh.
The trial was launched March 28, at Columbus Children's Hospital in Ohio, an affiliate of Ohio State University's School of Medicine. In the trial, six boys with DMD will receive replacement genes for an essential muscle protein.
Each of the boys will receive replacement genes via injection into a bicep of one arm and a placebo in the other arm. Neither the investigators nor the participants will know which muscle got the genes. After several weeks, an analysis of the injected muscle tissue's microscopic appearance, as well as extensive testing of the health and strength of the trial participants, will reveal whether gene therapy for DMD is likely to be safe and whether it's likely to result in persistent production of the essential protein in muscle cells.

Read the complete article here

Researchers get neurons and silicon talking

2006-03-29T08:41:00.000-05:00

From EurekAlert:
The ultimate applications are potentially limitless. In the long term it will possibly enable the creation of very sophisticated neural prostheses to combat neurological disorders. What's more, it could allow the creation of organic computers that use living neurons as their CPU.
Those applications are potentially decades away, but in the much nearer term the new technology could enable very advanced and sophisticated drug screening systems for the pharmaceutical industry.
"Pharmaceutical companies could use the chip to test the effect of drugs on neurons, to quickly discover promising avenues of research," says Professor Stefano Vassanelli, a molecular biologist with the University of Padua in Italy, and one of the partners in the NACHIP project, funded under the European Commission's Future and Emerging Technologies initiative of the IST programme.
NACHIP's core achievement was to develop a working interface between the living tissue of individual neurons and the inorganic compounds of silicon chips. It was a difficult task.
"We had a lot of problems to overcome," says Vassanelli. "And we attacked the problems using two major strategies, through the semiconductor technology and the biology."
With the help of German microchip company Infineon, NACHIP placed 16,384 transistors and hundreds of capacitors on a chip just 1mm squared in size. The group had to find appropriate materials and refine the topology of the chip to make the connection with neurons possible.
Biologically NACHIP uses special proteins found in the brain to essentially glue the neurons to the chip. These proteins act as more than a simple adhesive, however. "They also provided the link between ionic channels of the neurons and semiconductor material in a way that neural electrical signals could be passed to the silicon chip," says Vassanelli.
Once there, that signal can be recorded using the chip's transistors. What's more, the neurons can also be stimulated through the capacitors. This is what enables the two-way communications.
The project tested the device by stimulating the neurons and recording which ones fired using standard neuroscience techniques while tracking the signals coming from the chip.
The development of the interface and chip are crucial for this new technology, but problems remain. "Right now, we need to refine the way we stimulate the neurons, to avoid damaging them," says Vassanelli.
That's one of the problems the team hopes to tackle in a future project. Right now a proposal has been prepared which could tackle this and many other problems, including how to communicate with the neurons using genes.
"Genes are where memory come from, and without them you have no memory or computation. We want to explore a way to use genes to control the neuro-chip," says Vassanelli.
If NACHIP took the first crucial step towards a neuron-powered CPU, future work will pave the way for a genetically-powered hard disk.
"Europe is very well placed in this field of research, because it is essentially a multidisciplinary field, and we have multidisciplinary teams working on it," says Vassanelli. "We also have the infrastructure with institutes like the Max Planck Institute for Biochemistry in Martinsried, which is one of the world leaders in the field. Europe should be very proud of these resources. It gives us access to equipment and expertise that would be very hard to replicate elsewhere."

Arthritis

2006-03-28T14:11:00.000-05:00

The Houston Chronicle is running an article on the tissue engineering of new cartilage as a brute force therapy for the age-related damage of arthritis: "I have been researching this area of cartilage since 1984, and this is the most excited I have ever been about the work ... Athanasiou's group describes the first successful method of growing and molding cartilage into natural forms without requiring scaffolds, trellis-like arrangements upon which cells are seeded and grown. ... Using nothing but cartilage donor cells, Athanasiou's group grew dime-sized disks of cartilage nearly identical to that in the body. ... We're no longer talking about repairing a small lesion. Potentially, we're talking about effectively treating osteoarthritis by resurfacing the entire joint. I'm not saying we're there yet, but we're beginning to see that it's doable."

View the Article Under Discussion: http://www.chron.com/disp/story.mpl/health/3747377.html
Read More Longevity Meme Commentary: http://www.longevitymeme.org/news/

Reduced insulin in the brain triggers Alzheimer's degeneration

2006-03-24T09:43:00.000-05:00

Neuroendocrine disorder distinct from other types of diabetes
Providence, RI – By depleting insulin and its related proteins in the brain, researchers at Rhode Island Hospital and Brown Medical School have replicated the progression of Alzheimer's disease – including plaque deposits, neurofibrillary tangles, impaired cognitive functioning, cell loss and overall brain deterioration – in an experimental animal model. The study demonstrates that Alzheimer's is a brain-specific neuroendocrine disorder, distinct from other types of diabetes.
In the study, brain deterioration was not related to the pancreas, which regulates insulin for the body. When pancreatic insulin is deficient or the body fails to respond to it, the result is Type 1 or Type 2 diabetes. Previous work by the researchers with postmortem brain tissue of Alzheimer's patients showed a strong link between insulin depletion in the brain and Alzheimer's disease, raising the possibility that Alzheimer's is a neuroendocrine disorder, or a Type 3 diabetes.
"We have demonstrated that a loss of insulin in the brain triggers the onset of Alzheimer's, probably because as the brain loses insulin, the cells that require insulin to function and survive also eventually die. The consequences are increased oxidative stress, brain deterioration, loss of cognitive function, and a buildup of plaques and tangles in the brain – all hallmarks of Alzheimer's, says senior author Suzanne M. de la Monte, MD, MPH, a neuropathologist at Rhode Island Hospital and a professor of pathology and clinical neuroscience at Brown Medical School in Providence, RI.
"We now know that if you specifically target insulin and its actions in the brain, you could develop new treatments for this disease," de la Monte says.
The study is published in the current issue (Volume 9, Issue 1) of the Journal of Alzheimer's Disease (http://www.j-alz.com).
Researchers injected the brains of rats with Streptozotocin (STZ), a compound that when metabolized, destroys beta cells in pancreatic islets and produces diabetes. When injected directly into the brain, the treatment caused neurodegeneration, while the pancreatic islet cells remained intact. That is because insulin depletion produced by STZ was confined to the brain, just like what occurs in most cases of Alzheimer's.
"This study provides definitive evidence that impairments in insulin/IGF signaling and deficiencies in the corresponding growth factors can occur in the central nervous system (CNS) independent of Type 1 or Type 2 diabetes," the authors write.
As a result of the treatment, insulin and its IGF-I receptors were significantly reduced in the brain, triggering a cascade of neurodegeneration. Both insulin and IGF-I activate complex signaling pathways downstream, prompting energy metabolism and growth required for learning and memory, and inhibition of oxidative stress, which unchecked could trigger neurodegeneration. As insulin was depleted, neurons died and the brain dropped to half its size, a result of atrophy which is a prominent feature of Alzheimer's. At the same time, there was an increase in astrocytes and microglial cells, which are responsible for neuroinflammation, another critical and consistent feature of Alzheimer's and probably related to the increased amyloid deposition in the brain, the researchers say.
Also, there was increased activation of a kinase called GSK-3 beta. This kinase is overactive in Alzheimer's and triggers tau phosphorylation, which is known to be at the core of neurofibrillary tangles. The researchers had previously shown that tau is regulated by insulin and insulin-like growth factor (IGF-I). In the current research, they found that as insulin and IGF-I were depleted in the brain, the expression of GSK-3 beta increased, leading to oxidative stress and cell death.
While the link between insulin and tau had been established, researchers also looked at the connection between insulin and amyloid precursor protein gene expression, as increased levels could account for amyloid accumulation, or the buildup of plaques in the brain. They found that amyloid beta deposits in vessels and plaques did build up in the brain, and they suggest that these abnormalities occurred due to increased oxidative stress.
Another feature of Alzheimer's affected by impaired insulin signaling, acetylcholine deficiency, is linked to dementia and has long recognized as an early abnormality in Alzheimer's. The enzyme that makes acetylcholine, choline acetyltransferase (ChAT), was previously found to be regulated by insulin and IGF-1. In brains with Alzheimer's, impairment of insulin and IGF-I signaling mechanisms correlate with deficits in acetylcholine production. In this study, ChAT was markedly reduced in the experimental Alzheimer's model.
"Our previous work has shown that many of the important features of Alzheimer's – such as the accumulation of phosphorylated tau and the death of neurons – were somehow linked to insulin deficiency in the brain. This study shows that insulin is the controlling factor in all of these features of Alzheimer's disease," de la Monte says.
"The evidence suggests that impaired insulin and IGF signaling must be addressed in order to make significant progress in the treatment and prevention of Alzheimer's disease," she says.

Scientists One Step Closer To Cancer Vaccine

2006-03-24T08:31:00.000-05:00

Scientists at Karolinska Institutet in Sweden have helped to identify a molecule that can be used as a vaccination agent against growing cancer tumours. Although the results are so far based on animal experiments, they point to new methods of treating metastases.
The results are presented in the online edition of the prestigious scientific journal Nature Medicine, and represent the collaborative efforts of researchers at KI and Leiden University Medical Centre in Holland.
The study analysed an immunological cell, a T cell, which recognises other cells with defects common to metastasing ones. These defects (which are found in MHC class 1 molecules) allow the tumour cell to evade the "conventional" T cell-mediated immune defence.
The researchers have identified a short peptide molecule that the T cell in the study recognises. Using this peptide, the researchers can vaccinate and protect against the spread of tumours from different tissues, including melanoma, colon cancer, lymphoma, and fibrosarcoma.
"So far we've only conducted research on mice, so it's too early to get out hopes up too much," says research scientist Elisabeth Wolpert at the Microbiology and Tumour Biology Centre. "However, the study does point towards new possible ways of developing a treatment for advanced tumour diseases."
The newly published study is a continuation of an original discovery that first identified the TEIPP-T cell and that was presented in Ms Wolpert's doctoral thesis at Karolinska Institutet in 1998.
The spread of tumours, or metastases, is the most common cause of death from cancer.

Publication: Selective cytotoxic T-lymphocyte targeting of tumor immune escape variants, Nature Medicine, AOP (online edition), Thorbald van Hall, Elisabeth Wolpert, Peter van Veelen, Klas Kärre, Hans-Gustaf Ljunggren, Cornelis JM Melief, Rienk Offringa, et al.

The original news release can be found here.

Scientists one step closer to cancer vaccine

2006-03-21T14:15:00.000-05:00

###

Publication: Selective cytotoxic T-lymphocyte targeting of tumor immune escape variants, Nature Medicine, AOP (online edition), Thorbald van Hall, Elisabeth Wolpert, Peter van Veelen, Klas Kärre, Hans-Gustaf Ljunggren, Cornelis JM Melief, Rienk Offringa, et al
For further information, contact:
Elisabeth Wolpert on +46-70-7658308 or at elisabeth.wolpert@ki.se
Katarina Sternudd, KI Press Officer, on +46-8-524 838 95, +46-70- 224 38 95 or at katarina.sternudd@ki.se
via [EurekAlert!]

Astonishing Advances in Tissue Regeneration

2006-03-17T12:00:00.000-05:00

By Heather S. Oliff, PhD
A Genetic Approach to Regeneration
Researchers at the Wistar Institute in Philadelphia, PA, are studying a unique strain of mouse that can heal wounds by regeneration. After a hole is pierced in the mouse’s ear (a typical laboratory identification procedure), it closes with no evidence that a hole was ever present.¹⁶ These animals, known as Murphy/Roths/Large mice, or MRL mice, are so named to denote the two scientists who originally bred them, as well as their unusually large size. MRL mice are genetically unique, and scientists are researching them to elucidate the genetics of regeneration, hoping to gather information that can be used to help humans.¹⁷
When the Wistar scientists induced heart injury in both MRL mice and typical mice, they found that the MRL mouse heart returned to normal, whereas the typical mouse heart was scarred.¹⁸ Human hearts scar following injury from heart attack, and the scarring response contributes to chronic heart disease and death.¹⁹ The healing response in the MRL mouse, however, differed greatly from that of the typical mouse. The MRL mouse displayed early movement of cardiomyocytes into the wound site, and DNA synthesis and proliferation of these cells.¹⁸ The MRL mouse heart also demonstrated better revascularization (restoration of blood supply) at the site of injury, which is necessary to help cells thrive and avoid death. According to the scientists, the MRL mouse studies demonstrate that “mammalian hearts have significant capacity to regenerate.”¹⁸
The Wistar scientists are now working to identify which genetic and biochemical factors are involved in this regenerative response. They have already identified areas on several chromosomes that control wound closure and are involved in regeneration of the MRL mouse ear tissue.^19,20 It is unclear whether these same chromosomes are responsible for regenerating the MRL heart.¹⁸
A potential key mediator of regeneration is the family of enzymes known as the matrix metalloproteinases. These protein-digesting enzymes degrade the collagen that helps form scar tissue. They occur in immune cells, along with another family of molecules called the tissue inhibitors of metalloproteinase, which inhibit matrix metalloproteinases. After an injury, neutrophils that contain matrix metalloproteinases and tissue inhibitors of metalloproteinase enter the wound. Regeneration or scarring occurs depending on whether matrix metalloproteinases or tissue inhibitors of metalloproteinase dominate. The MRL mouse ear wound has a more active form of matrix metalloproteinases and lower levels of tissue inhibitors of metalloproteinase than the typical mouse ear wound.¹⁹ This combination promotes a regeneration process rather than a scarring process in the MRL mouse.¹⁹
The scientists also looked at the ability of MRL mice to heal central nervous system injuries.²² In the MRL mice, the matrix metalloproteinase response was temporarily increased following a brain injury, but the brain was not repaired differently than that of the typical mouse.²² The researchers hypothesize that the central nervous system has mechanisms to decrease the matrix metalloproteinase response, and that the tendency to scar blocks regenerative healing.^17,19,22 Discovering how to prevent the formation of scar tissue may eventually make it possible to regenerate the heart, heal chronic wounds and burns, repair spinal tissue, and promote organ replacement.

References
16. Clark LD, Clark RK, Heber-Katz E. A new murine model for mammalian wound repair and regeneration. Clin Immunol Immunopathol. 1998 Jul;88(1):35-45.
17. Bedelbaeva K, Gourevitch D, Clark L, et al. The MRL mouse heart healing response shows donor dominance in allogeneic fetal liver chimeric mice. Cloning Stem Cells. 2004;6(4):352-63.
18. Leferovich JM, Bedelbaeva K, Samulewicz S, et al. Heart regeneration in adult MRL mice. Proc Natl Acad Sci USA. 2001 Aug 14;98(17):9830-5.
19. Heber-Katz E, Leferovich J, Bedelbaeva K, Gourevitch D, Clark L. The scarless heart and the MRL mouse. Philos Trans R Soc Lond B Biol Sci. 2004 May 29;359(1445):785-93.
20. McBrearty BA, Clark LD, Zhang XM, Blankenhorn EP, Heber-Katz E. Genetic analysis of a mammalian wound-healing trait. Proc Natl Acad Sci USA. 1998 Sep 29;95(20):11792-7.
21. Heber-Katz E, Chen P, Clark L, et al. Regeneration in MRL mice: further genetic loci controlling the ear hole closure trait using MRL and M.m. Castaneus mice. Wound Repair Regen. 2004 May;12(3):384-92.
22. Hampton DW, Seitz A, Chen P, Heber-Katz E, Fawcett JW. Altered CNS response to injury in the MRL/MpJ mouse. Neuroscience. 2004;127(4):821-32.

New Artificial Muscles Are Powerhouses

2006-03-17T09:23:00.000-05:00

New Designs Are More Than 100 Times Stronger Than Natural Muscle

By Miranda Hitti
WebMD Medical News

Reviewed By Louise Chang, MD
on Thursday, March 16, 2006

March 16, 2006 -- The latest artificial muscles make natural muscles look like weaklings, according to a study in Science.
Researchers invented two types of artificial muscles that use high-energy chemical fuels -- such as methanol and hydrogen -- instead of batteries. The inventions can outwork natural muscles, with one design showing 100 times the strength of natural muscles.
The scientists included Von Howard Ebron, PhD, and Ray Baughman, PhD. Both work at the University of Texas at Dallas.
The invention should lead to powerful devices that truly "keep on going," states a journal editorial. But the new muscles don't yet give the "exquisite control" needed for tasks like catching and throwing balls, the editorial also notes.
Unplugging Artificial Muscles
Artificial muscles and electrical motors in robots and prosthetic limbs "are typically battery powered, which severely restricts the duration of their performance and can necessitate long inactivity during battery recharge," write Ebron and colleagues.
"Because of high electrical power needs, some of the most athletically capable robots cannot freely prance around because they are wired to a stationary power source," the scientists add.
Their artificial muscles work differently, tapping chemical energy in fuels instead of relying on batteries. One model converts chemical energy in fuels to electrical energy for movement or storage. The other model mixes fuel and oxygen to create heat for energy.
The latter version is "especially easy to deploy in robotic devices," Baughman says in a news release. "Students and scientists of all ages will be working on optimizing and deploying our artificial muscles," he predicts.
"The approach is not without challenges, but it could transform the way complex mechanical systems are built," writes editorialist John D. Madden, PhD. Madden works at Canada's University of British Columbia in Vancouver. Developing fine control over such artificial muscles is one of those challenges, Madden notes.

Nanotechnology May Repair Damaged Brains

2006-03-14T12:50:00.000-05:00

TUESDAY, March 14 (HealthDay News) -- Rodents blinded by brain damage had their vision partially restored within weeks after being treated with nanotechnology developed by bioengineers and neuroscientists at the Massachusetts Institute of Technology.
The findings provide evidence that similar strategies might someday work in humans.
"If we can reconnect parts of the brain that were disconnected by stroke, then we may be able to restore speech to an individual who is able to understand what is said but has lost the ability to speak," study co-author Rutledge G. Ellis-Behnke, research scientist in MIT's department of brain and cognitive sciences, said in a prepared statement.
This method uses an extremely tiny biodegradable scaffold that provides brain cells with a place to re-grow -- like a vine on a trellis -- in the damaged area of the brain. This is the first study to use nanotechnology to repair and heal the brain and restore function in a damaged brain region. The approach may one day help treat stroke patients and people with spinal cord and traumatic brain injuries.
The findings appear online this week in the journal Proceedings of the National Academy of Sciences.
The study included young and adult hamsters with severed neural pathways. The animals were injected with a solution containing certain kinds of peptides (protein fragments) that create a mesh or scaffold of tiny, interwoven fibers. Brain cells are able to grow on this mesh.
Within about six weeks, the hamsters had regained useful vision and the adults' brains responded as well as the younger animals' brains.
"This is not about restoring 100 percent of damaged brain cells, but 20 percent or even less may be enough to restore function, and that is our goal," Ellis-Behnke said.
More information
The Brain Injury Association of America has more about types of brain injury.
Copyright Â© 2006 HealthDay. All rights reserved.

The Guru of Anti-Aging

2006-03-14T12:47:00.000-05:00

MARCH 20, 2006

COVER STORY

Online Extra: The Guru of Anti-Aging

There's plenty doctors can do to control the effects of old age, says a leading light in the anti-aging medical movement

Since 1981, Dr. Ronald M. Klatz has served as the chief champion of anti-aging medicine. He coined the very term "anti-aging." In 1992, he became the founder and president of the American Academy of Anti-Aging Medicine, which he describes in his Internet bio as a "medical organization dedicated to the advancement of technology to detect, prevent, and treat aging-related disease and to promote research into methods to retard and optimize the human aging process." He isn't shy about expressing his support for the entire anti-aging arsenal of tools, including controversial drugs such as human growth hormone (HGH). He's even written books on the topic, including Grow Young with HGH, Ten Weeks to a Younger You, and Hormones of Youth.

During a telephone interview with BusinessWeek Science Editor Arlene Weintraub, Klatz discussed the history of anti-aging medicine, the controversies that have followed its success, and his hopes for the future of this nascent field. Following are edited excerpts from their conversation.

What inspired you to get into anti-aging medicine?
The goal of medicine is to prolong life. That's what most of us doctors go into medicine to accomplish. One day I looked in the mirror, and I saw wrinkles. I said, "Physician, heal thyself." Until the 1980s, scientists didn't have a clue as to how or why we age. Then it became very clear that medicine was developing new technologies for dealing with genetic disorders and chronic degenerative diseases. Many of these diseases occur in the aged. I felt that if medicine could control the metabolic effects of aging, we could control aging itself.

There's been a bit of controversy about the use of HGH, which was originally approved to promote growth in short children and to treat just a handful of diseases in adults. What is the role of HGH in the context of the entire anti-aging arsenal?
HGH is the most extreme example in anti-aging medicine. About 10% of patients who are on the full regimen are taking HGH.

Do you believe HGH reverses aging?
This is a matter of semantics. It does reverse bone loss, muscle loss, and it improves hydration of tissue. We're reversing the physical processes of aging.

What's your response to critics who say HGH isn't safe for otherwise healthy adults?
When they say it's not safe, it's as if they're screaming "fire" in a crowded theater. There will still be critics who beat their chests and come up with bogus research saying there are side effects. Those only occur when someone's taking massive amounts. In adults we're merely replacing the hormone to the normal level of a 30-year-old. That's just one-third to one-seventh of the dose that's been shown to be safe in children. This drug has been used clinically over the last 20 years in hundreds of thousands of young people and tens of thousands of adults. There is no published literature showing that HGH has caused any permanent side effects, or death. It's one of the best-researched drugs out there. The critics shouldn't make [danger] proclamations without a scientific basis. Show me the studies that say these treatments cause cancer or diabetes.

What else helps reverse the ravages of age?
There's no single "age reversal" drug, but we have a lot of things that work. Exercise, for example, can change the biomarkers of aging. If you use testosterone or estrogen, it might help maintain the health of the cells in your body. That can improve the biomarkers of aging. Aging is not one global thing. We haven't yet found a single control switch.

How quickly is the field of anti-aging medicine growing?
AAM has grown from 12 physician members to 17,500 in 85 countries. We'll have 26 seminars in 2006, where we'll train 30,000 doctors worldwide. With 1,500 physicians certified in anti-aging medicine, we think it's the fastest-growing medical certification program in history.

What's your ultimate hope for how the public might someday view anti-aging medicine?
I believe that one day it will be considered malpractice for any physician not to do what anti-aging physicians do today.

Copyright 2000- 2006 by The McGraw-Hill Companies Inc.
All rights reserved.

Cochlear Implants Aim for Age-Related Loss

2006-03-14T12:44:00.000-05:00

We're working on being able to replace the body piece by piece. We have eyes, and ears (now with hybrid implants), and we're working on being able to replace organs with 3 dimensional structures. We've been able to replace limbs for some time, although they have been relatively crude until recently. I don't think it will be long before the only thing left will be the brain.

By LAURAN NEERGAARD, AP Medical WriterMon Mar 13, 6:01 PM ET

Cochlear implants may not be just for the profoundly deaf anymore: Iowa scientists are developing the next generation, a "hybrid implant" to combine the best of bionics with regular hearing aids for age-related hearing loss.

If it works — and early study results are promising — it one day may help thousands of older Americans whose hearing is progressively fading. The key difference: Unlike regular cochlear implants, the hybrid model would let people keep their natural music appreciation even as it helps them hear speech more clearly again.

That's what attracted attorney Gordon Gross, a concert lover, to the experimental device five months ago. With his hearing aids at full blast, Gross could conduct one-on-one conversations. But he could barely distinguish sentences from the background noise during the meetings required for his job.

"Most people in my situation smile a lot, fake what they hear," says Gross, 74, of Buffalo, N.Y.

He's still undergoing required training to learn to recognize speech with the implant. But Gross recently popped in a "Phantom of the Opera" CD and noticed that, "where before I wouldn't understand virtually anything, I'm now beginning to pick up words and phrases. It is very exciting."

How does it work? Like tuning a piano, says Dr. Bruce Gantz, an otolaryngologist at the University of Iowa who invented the hybrid model now being tested at 26 medical centers around the country.

Normally, microscopic hair cells in the cochlea, the snail-shaped inner ear, pick up vibrations and convert them into electrical impulses that the brain recognizes as different sounds. Hairs in the deepest part of the cochlea pick up low-frequency sounds, such as music. Hairs at the cochlea's entrance pick up high-frequency sounds, including speech.

With age-related hearing loss, people tend to first lose high-frequency hearing. Initially, specific consonants disappear — they no longer can discriminate, say, a "c" from a "t." They stumble over more and more words until they're unable to decipher entire sentences, especially when there's competing noise. Hearing aids turn up the volume for all sounds, not just speech, and thus eventually quit helping.

"If you filter those (consonants) out to a great extent, you can make the sound as loud as you like and it's still incomprehensible," explains Dr. James Battey, who directs the National Institutes of Health's hearing-loss division.

Enter cochlear implants. Surgically placed behind and in the ear, the implant itself turns sound into electrical impulses that directly activate the hearing nerve, allowing the deaf to hear. They've proven particularly beneficial for deaf babies and young children, dramatically improving their ability to learn to speak and comprehend language normally.

But for people who aren't completely deaf, cochlear implants have a big catch: Snaking the electrode deep into the cochlea destroys whatever hair cells still live in the inner ear. If your only problem is detecting high-frequency sounds, a regular cochlear implant would destroy your ability to hear low-frequency sounds normally, such as music or the pitch that distinguishes one speaker from another.

Gantz's solution: Make the electrode shorter, so it only substitutes for the hearing that's already lost. Pair it with a regular hearing aid to amplify their remaining low-frequency hearing, and people just might hear again more like they did years earlier.

So far, about 60 patients have received the hybrid implant, manufactured by Cochlear Americas. About 10 have had it for more than a year. On standard hearing tests, those patients understand 70 percent of words a year after the implant — up from 25 percent before the surgery, Gantz says. That comprehension seems to continue improving as the brain rewires itself to better recognize the electronic signals.

More research is needed before the company seeks Food and Drug Administration approval. But NIH, which is partly funding Gantz's work, and independent specialists call the hybrid implant a potentially important step.

"It addresses patients who are in a very difficult middle ground," says Dr. John Niparko of Johns Hopkins University. "It allows them to perceive the richness of sound through the cochlear zones that are still working," while compensating for the "dead zones."

The brain does have to adjust to decoding electronically generated sound. Users require training, and some describe an echo effect for a few weeks. "It was almost as if I was hearing from two different places," recalls Paula Fuller, 61, of Haver Hill, Iowa.

But within a month of her January 2000 implant, she was hearing sounds she hadn't heard in years — birds chirping, the dialogue in a movie — and no longer avoiding social situations for fear she couldn't converse.

RE: World faces challenge as life expectancies lengthen, scientist says

2006-02-21T18:44:00.000-05:00

In the 21st century, state-of-the-art anti-aging technologies may extend human lifespans at an unprecedented rate, bringing with them a host of social and economic challenges, says biologist Shripad Tuljapurkar of Stanford University. He will present his findings on Feb. 17 at the annual AAAS meeting in St. Louis.

[Via EurekAlert! - Medicine and Health]
This article on EurekAlert concerns a paper written by Shripad Tuljapurkar, concerning how old age will affect the economy. My reading of the initial article leads to several concerns with the assumptions. The first concern is that it is assumed that 20 years will be added to healthy life, bringing our life expectancy to about 100, but there is no assumption that people will continue to work for 20 more years, instead it is assumed (with all that normally goes with that saying) that people will continue to retire at age 65, and the sit on their ass for 35 years drawing social security. I find this a ludicrous assumption for a couple of reasons. One is that if anyone under age 50 is counting on social security to provide for their retirement, then they are an idiot, and I find it hard to believe there are that many idiots in the country. The second is that someone could sit around doing nothing for that long. I know I can't see it. I can see maybe taking periods of a year or more off at a time, as by that time you wouldn't have the monetary obligations that a family bring, so you would be able to save up some cash to be able to take extended vacations, but I for one would get bored doing nothing all the time. The other problem I have is with the social security program in general, the fact that the government thinks they need to take responsibility for us as we get old. I am perfectly capable of planning and saving money for myself (which would be a bit easier if the government weren't taking 12% out of my check that I never expect to see again), and I expect to have to take responsibility for myself. That's what this country was founded on, life, liberty, and the pursuit of happiness. Liberty being the freedom and responsibility to have to take care of yourself. Too many people these days forget the responsiblity that freedom brings in addition to the choice.

I have, however, seen additional articles that Shripad Tuljapurkar is advocating raising the age of retirement to 85, which seems to be a somewhat reasonable compromise. I would however like to see people retire both when they want to and when they are financially able to do so, instead of being coddled like children.