Organiser's Note: This talk was cancelled by the presenter, and therefore no video is available.
Activation of SIRT1, an NAD+-dependent deacetylase sensitive to nutrient availability, promotes longevity in animals ranging from yeast to mammals. Here we show treatment with SRT1720, a potent and specific activator of SIRT1, extends the mean and maximum lifespan of C57/Bl6 mice fed a high fat diet (HFD) starting after 1 year of age. Mean lifespan increased from 95 weeks in the HFD to 105 weeks when the HFD was supplemented with SRT1720 at a dose of 30 mg/kg and 115 weeks at a dose of 100 mg/kg. This increase is accompanied by a variety of metabolic effects. Measures of glucose homeostasis showed fasting blood glucose is reduced by SRT1720 and insulin sensitivity as measured by the HOMA is enhanced. Body composition analysis by NMR revealed reduced fat mass and increased lean to fat mass ratio in the mice consuming SRT1720. Organ weights in the liver, heart and kidney were also reduced in the treated groups. These data provide further support of SIRT1 as a target for potential calorie restriction mimetics and for the treatment of metabolic disorders associated with high fat diets.