Early but intriguing research on mice suggests a new mechanism of aging, and possibly a way to stall it.

Drugs designed to target one aspect of aging also seem to help repair DNA damage and regulate gene activity, preventing them from going haywire with the stresses of time.

"In principle, we now could have a way of reversing the effects of aging," said David Sinclair, a Harvard University gerontologist and co-founder of Sirtris Pharmaceuticals, a company best-known for its development of an experimental drug called resveratrol.

Resveratrol and similar compounds activate an enzyme called SIRT1. The enzyme rejuvenates mitochondria, the machines that power our cells. Mitochondrial breakdown has been associated with many age-related diseases, including heart disease, diabetes and dementia. Several labs in addition to Sirtris are researching compounds that target mitochondria.

The new findings suggest that SIRT1 fixes DNA in addition to mitochondria.

Sinclair's team found that unless SIRT1 enzymes gathered at sites where DNA had started to unravel, other DNA repair proteins failed to arrive. This allowed damage to progress, eventually causing dormant genes to come alive, a process called deregulation.

Some researchers think gene deregulation is a cause of aging: As cells get older, they produce less SIRT1, ostensibly becoming less able to repair faulty DNA and suppress the dormant genes.

But in mice either given resveratrol or genetically engineered to produce extra SIRT1 on their own, repairs went smoothly and quickly.

"One idea of why we age is that DNA becomes damaged or mutated," said Sinclair, lead author of the research published Wednesday in Cell. "But perhaps the main culprit is the effect of genes switching on and off, and that should be reversible."

But as with any animal study of a new mechanism for something as complex as aging, caution is advised in extrapolating from the results.

"We have a long way to go before applying this to humans," said

University of Southern California gerontologist Valter Longo, who was not involved in the study.

The exact role of gene activation in aging is not entirely clear. And while Sinclair's work showed that cancer-prone mice lived 40 percent longer than usual after SIRT1 stimulation, they didn't test its benefits on healthy mice.

Sinclair said that such tests are planned, as are experiments on elderly mice designed to see whether SIRT1 stimulation causes genetic patterns to revert to youthful states.

He also hopes to determine if other members of the SIRT1 enzyme family, known as sirtuins, have similar roles.

"We think this is just the tip of the iceberg, and that SIRT1 is just the first of many proteins that get reshuffled during aging," he said.

*

SIRT1 Redistribution on Chromatin Promotes Genome Stability but Alters Gene Expression during Aging * [Cell]**

Image: An example of DNA damage in aging cells. On the left, a chromosome breaks apart; on the right, a chromosome fuses together

/ Cell

*

*

See Also:

WiSci 2.0: Brandon Keim's Twitter stream and Del.icio.us feed; Wired Science on Facebook.