Resveratrol Could also Help Repair DNA Damages

by Gopalan on Dec 1 2008 2:40 PM

Resveratrol not only rejuvenates mitochondria, but could also repair DNA damages. Mitochondria in our cells is targeted as its breakdown is been associated with many age-related diseases, including heart disease, diabetes and dementia.

The enzyme activated by resveratrol and similar compounds, SIRT1, can also help fix DNA, it has now been found.

"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 resveratrol.

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, writes Brandon Keim on Wired.

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.