Fat mice live longer with resveratrol.

Nicholas Wade points to a study by de Cabo, Sinclar, and colleages that studies the effect of a drug, SRT-1720, that has extends the lifespan of mice on a low calorie diet, but at much lower (less toxic) concentrations than resveratrol. Benefits of the drug are much easier to demonstrate in mice under physiological stress like obesity than in normal mice. The studied found that obese animals taking the drug lived 44 percent longer, on average, than control obese animals. From Wade's comments:

The sirtuins help bring about the 30 percent extension of life span enjoyed by mice and rats that are kept on very low-calorie diets. Since few people can keep to such an unappetizing diet, researchers hoped that doses of resveratrol might secure a painless path to significantly greater health and longevity...But large doses of resveratrol are required to show any effect, so chemical mimics like SRT-1720 were developed to activate sirtuin at much lower doses...Sirtuins have proved to be highly interesting proteins, but the goal of extending life span was set back last year when extensive trials of resveratrol showed it did not prolong mice’s lives, although it seemed to do them no harm. Another blow came in 2009, when biologists at Pfizer reported that SRT-1720 and other resveratrol mimics did not activate sirtuins and did not have any beneficial effects in fat mice...The report by Dr. de Cabo and his colleagues may do much to rescue SRT-1720 from this shadow. They found that SRT-1720 offered substantial benefits to the fat mice, with no signs of toxicity. Unlike the Pfizer study, which was short term, they followed large groups of mice for over three years.

Here is the article abstract:

Sirt1 is an NAD+-dependent deacetylase that extends lifespan in lower organisms and improves metabolism and delays the onset of age-related diseases in mammals. Here we show that SRT1720, a synthetic compound that was identified for its ability to activate Sirt1 in vitro, extends both mean and maximum lifespan of adult mice fed a high-fat diet. This lifespan extension is accompanied by health benefits including reduced liver steatosis, increased insulin sensitivity, enhanced locomotor activity and normalization of gene expression profiles and markers of inflammation and apoptosis, all in the absence of any observable toxicity. Using a conditional SIRT1 knockout mouse and specific gene knockdowns we show SRT1720 affects mitochondrial respiration in a Sirt1- and PGC-1α-dependent manner. These findings indicate that SRT1720 has long-term benefits and demonstrate for the first time the feasibility of designing novel molecules that are safe and effective in promoting longevity and preventing multiple age-related diseases in mammals.