Calorie reduction and life span extension: a genetic pathway in the fly

Our studies have led to the proposal of a genetic/biochemical pathway for the life span extending effects of calorie restriction. A decrease in total calories or mutations in Indy or other triggers that similarly alter the metabolic state of the fly decrease Rpd3 activity, increase Sir2 activity, reduce p53 activity, and extend life span. Our success in predicting the life span extending effect on flies of the Sir2 activator resveratrol suggest that knowledge of this pathway will be valuable for identifying additional interventions for extending life span in flies and other species, including humans.