Hope For Anti-Aging Pill Restored As Controversy On Life-Extending Red Wine Ingredient Resolved

Why alcoholics look so young.

A study in the May issue of the Cell Press journal Cell Metabolism appears to offer vindication for an approach to anti-aging drugs that has been at the center of heated scientific debate in recent years. The new findings show for the first time that the metabolic benefits of the red wine ingredient known as resveratrol evaporate in mice that lack the famed longevity gene SIRT1.

"Resveratrol improves the health of mice on a high-fat diet and increases life span," said David Sinclair of Harvard Medical School. The question was how.

Resveratrol is a dirty molecule, he explained. Its benefits had been attributed largely to its actions on SIRT1, based on studies in yeast, worms, and flies, but the naturally occurring ingredient has other effects; it influences dozens of proteins, and some evidence had pointed to the importance of another well-known gene (called AMPK) for resveratrol's metabolic benefits. That called into question not only the biology, but also whether SIRT1-targeted drugs in development were aimed in the wrong direction. (Those doubts and other factors led the pharmaceutical company Sirtris to halt its last clinical trial of resveratrol last year.)

Answers were hard to come by in mice, because animals lacking SIRT1 altogether don't survive. Sinclair and his colleagues have now overcome that obstacle by producing mice in which the SIRT1 gene can be completely turned off in adults. They've discovered that those SIRT1-deficient adult mice don't enjoy the benefits of resveratrol.

Alcoholic mice, too.