Calorie Restriction Promotes Mammalian Cell Survival by

A major cause of aging is thought to result from the cumulative effects of cell loss over time. In yeast, caloric restriction (CR) delays aging by activating the Sir2 deacetylase. Here we show that expression of mammalian Sir2 (SIRT1) is induced in CR rats as well as in human cells that are treated with serum from these animals. Insulin and insulin-like growth factor 1 (IGF-1) attenuated this response. SIRT1 deacetylates the DNA repair factor Ku70, causing it to se-quester the proapoptotic factor Bax away frommitochondria, thereby inhibiting stress-induced apoptotic cell death. Thus, CR could extend life-span by inducing SIRT1 expression and promoting the long-term survival of irreplaceable cells. In mammals, caloric restriction (CR) delays the onset of numerous age-associated dis-eases including cancer, atherosclerosis, and diabetes, and can greatly increase life-span (1). The molecular mechanisms underlying this effect are not known. In the buddin