Sirtuin is a NAD+-dependent protein deacylase that can cleave off acetyl and other acyl groups from the ε-amino group of lysines in histones and other substrate proteins. Studies have shown that Sirtuin is an important target for regulating diseases by calorie restriction (CR). It participates in development of various human age-related diseases， including metabolic syndrome， cancer， cardiovascular disease and neurodegenerative disease. In recent years， numerous evidences indicate that various compounds activate Sirtuin to simulate the effects of CR in preventing and regulating diseases. To better understand the underlying mechanism of Sirtuin in these diseases， and to screen Sirtuin-activating food components， this article focuses on the latest developments in Sirtuin-regulated signaling pathways， and summarizes the mechanism of foodborne Sirtuin activators in disease prevention.