Calorie Restriction Increases Life Span: A Molecular Mechanism

Calorie restriction increases the life span of many organisms, from yeast to mammals. In yeast, the life span gene affected by calorie restriction is Sir2 (silent information regulator 2). In mammals, Sirt1, an ortholog of Sir2, controls the metabolism of white adipose tissue. Calorie restriction activates Sirt1, and the expressed Sirt1 protein inhibits the action of peroxysome proliferator-activator receptor gamma (PPARgamma), the nuclear receptor that promotes adipogenesis. The effect is lipolysis and loss of fat. Lowering of adiposity appears to be one mechanism whereby calorie restriction affects life span.