Wrinkled cell nuclei may make us age

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.