"Researchers have found new evidence showing that resveratrol a compound found in red wine may play a role in preventing cell aging. The study in rodents found that when mice had a particular gene  SIRT  knocked out or turned off resveratrol had no effect on them. But tests of muscle tissue in mice with a normal SIRT gene that were given resveratrol found that the substance boosted mitochondrial function. Mitochondria provide the energy that cells need to function. A decrease in mitochondrial energy production has been linked to a variety of diseases including diabetes and Alzheimers disease as well as to the aging process itself said senior study author David Sinclair a professor of genetics at Harvard Medical School in Boston. But dont go reaching for that Chianti yet. Yes resveratrol is found in the skin of red grapes. But the amounts we gave to our mice would be like drinking  glasses of red wine a day Sinclair said. Instead the goal is to develop synthetic resveratrol compounds that activate SIRT and could be taken as medication. My colleagues are in the middle of developing better molecules that we hope will be medicines that will be used to treat diseases of aging not to extend lifespan though that may be a side effect Sinclair said. The study is in the May  issue of Cell Metabolism. While previous studies have also suggested that resveratrol may have antiaging properties the precise mechanism of resveratrol has been controversial. Several studies including work with yeast worms and flies have found that resveratrol acts on a class of seven genes known as sirtuins and in human cells SIRT in particular. But other researchers have argued that resveratrol may work by activating a separate energy pathway called AMPK which is also related to mitochondrial energy production but does not involve sirtuin genes. Testing the effect of resveratrol on SIRT in mice was difficult Sinclair said. Mice that have their SIRT gene deleted are born with developmental defects and are unsuitable for experiments he explained. So Sinclair and two graduate students Nathan Price and Ana Gomes worked for years to come up with a method for knocking out SIRT in healthy adult mice. Our paper found you absolutely require the SIRT gene for resveratrol to improve the metabolism of the mice Sinclair said. The paper also showed that the AMPK pathway was activated in mice given high doses of resveratrol yet there was no benefit to mitochondrial function. There was no effect on AMPK in mice given a lower dose of resveratrol. Sinclair is cofounder and a consultant for Sirtris Pharmaceuticals Inc. which is developing resveratrollike molecules for use as treatment for agerelated diseases. In  according to news reports the company which is owned by GlaxoSmithKline halted clinical trials of resveratrol but Sinclair said the company continues to develop improved synthetic molecules. George Vlasuk CEO of Sirtris said the new findings offer the first definitive evidence for a direct link between SIRT and the metabolic benefits of resveratrol. The work by first author Price et al. strongly supports the basic rationale being pursued at Sirtris which focuses on the development of smallmolecule compounds that directly activate the enzymatic activity of SIRT as a new therapeutic approach to many diseases of aging Vlasuk wrote in an email to the journal. Philippe Marambaud an investigator at the LitwinZucker Center for Research in Alzheimers Disease and Memory Disorders at the Feinstein Institute for Medical Research in Manhasset N.Y said the new research adds to a body of evidence that resveratrol can potentially combat aging by boosting mitochondrial activity. In this study by using an elegant adultinducible SIRT knockout mouse model the authors now provide compelling evidence that SIRT is required in vivo in the animal for the effect of resveratrol on AMPK activation and on mitochondrial function Marambaud said. While studies involving animals can be useful they frequently fail to produce similar results in humans. A mouse model is not a human being especially when you are genetically manipulating this animal model you want to be very careful Marambaud said. This field has been extremely controversial. We should be very careful about claiming the importance of resveratrol for medical purposes. We have to wait and see but this study is a big step forward. More information The U.S. Centers for Disease Control and Prevention http has more on healthy aging. SOURCES David Sinclair Ph.D. professor of genetics Harvard Medical School Boston Philippe Marambaud Ph.D. investigator LitwinZucker Center for Research in Alzheimers Disease and Memory Disorders Feinstein Institute for Medical Research Manhasset N.Y. May   Cell Metabolism"