Caloric restriction(CR) can delay aging and the onset of aging-related diseases. Sirtuin plays a key role in the aging process regulated by CR because of its ability to sense the metabolic status and to integrate into adaptive transcriptional outputs. Sirtuin regulates the aging process by altering protein activity and stability through lysine acetylation. Moderate CR in yeast influences replicative lifespan and chronological lifespan mainly by increasing the NAD⁺/NADH ratio and regulating the level of nicotinamide. Similar mechanism also exist among Caenorhabditis elegans and Drosophila melanogasters. SIRT1 protein level increases in response to CR in mammals, leading to an increase in PNC1/Nampt expression, which favors the synthesis of NAD⁺ from NAM, potentially acting as a major mechanism to drop the leash of SIRT1 inhibition. NO up-regulates SIRT1 and mitochondrial biogenesis. Cellular and organism's senescence may be influenced through the deacetylation of histone, p53, NES1, FOXO by SIRT1, indicating sirtuin and its homologous analogues play important roles in aging process and lifespan extension under CR in different organisms.