Sirtuins: Nodes Connecting Aging, Metabolism and Tumorigenesis

Sir2-like proteins, known as sirtuins, have been under a spotlight in the realm of aging because of their positive effect on longevity in Saccharomyces.cerevisiae. Because Sir2 has been identified as a NAD⁺-dependent histone deacetylase, researchers have attributed its lifespan-extending utilities to gene silencing. Similar phenomena are found in multicellular eukaryotes by seemingly different mechanisms. In mammals, seven sirtuin homologs (SIRT1-7) have been identified, with varied cellular locations and molecular functions. Sirtuins target a wide spectrum of molecules for diversified post-translational modifications, thereby exerting multiple physiological benefits. The roles of sirtuins in cancer are still ambiguous, although they have been extensively studied. In this review, we summarize the multiple physiological roles played by sirtuins and their putative mechanisms, especially in cancer.