Sirtuins are NAD-dependent deacetylases that are highly conserved from bacteria to human and SIR2 was originally shown to extend lifespan in budding yeast (Imai et al., 2000; Kaeberlein et al., 1999). Since then, sirtuins have been shown to also regulate longevity in other lower organisms, such as flies and worms (Tissenbaum and Guarente, 2001; Rogina and Helfand, 2004). In mammals, there are seven sirtuins (SIRT1-7). All mammalian sirtuins contain a conserved NAD-binding and catalytic domain, termed the sirtuin core domain, but differ in their N-and C-terminal domains (Frye, 2000). They have different specific substrates and biological functions, and are found in various cell compartments. The fact that sirtuins require NAD for their enzymatic activity connects metabolism to aging and aging-related diseases. In this Cell Science at a Glance article, we summarize the recent data related to the role of sirtuins in aging and aging-related diseases, and describe the underlying molecular mechanisms.