Harvard Medical School professor of genetics David A. Sinclair and his associates confirm in the May, 2012 issue of the journal Cell Metabolism that the red wine compound resveratrol does indeed impact the longevity gene SIRT1, as well as affect other proteins. “This study provides the first in vivo evidence that beneficial effects of resveratrol on mitochondrial function require SIRT1,” the authors announce.
Earlier research involving yeast, worms and flies had indicated that resveratrol targeted the sirtuin family of genes of which SIRT-1 is a member, but the findings, which were not duplicated in animals due to the fact that those in which the gene for SIRT1 is knocked out don’t survive, had been called into question. The concern led one pharmaceutical company to suspend some of its research involving the compound. However, Dr Sinclair’s team has now produced mice in which SIRT1 can be completely disabled during adulthood via administration of the drug tamoxifen and have shown that these animals don’t experience improved mitochondrial function in response to resveratrol, while mice with normal SIRT1 exhibit increased mitochondrial formation and function. They determined that resveratrol targets SIRT1 at moderate doses and that other molecules, such as AMPK (which is also related to the mitochondria), are targeted at higher doses.
“Resveratrol improves the health of mice on a high-fat diet and increases life span,” stated Dr Sinclair. “The results were surprisingly clear. Without the mitochondria-boosting gene SIRT1, resveratrol does not work.”
“It’s standard when you study molecules that you use the lowest dose that gives you an effect because of the risk of hitting other things if you use too much,” he noted. “But for the downstream benefits on energy, you still need SIRT1. Our paper shows that SIRT1 is front and center for any dose of resveratrol.”