SIRT1 (sirtuin 1) is the human ortholog of the yeast Sir2 (silent information regulator 2) protein, which is implicated in lifespan extension in model organisms, such as yeast, worms and flies. It is an NAD+-dependent protein deacetylase with over two dozen known substrates that affect a wide variety of cellular processes, ranging from metabolism, cell cycle, growth and differentiation, inflammation, senescence, apoptosis, stress response and aging. Even though SIRT1 has been linked to calorie restriction-mediated longevity in model organisms, the mechanism by which it extends lifespan in mammals is not fully understood. A growing body of evidence suggests a role of SIRT1 in maintaining energy and nutrient homeostasis, thereby linking its anti-aging property to its role in metabolism.