Sirt1 as a key regulator orchestrating the response to caloric restriction

Although it was discovered more than 70 years ago that caloric restriction (CR) extends the life span of rodents, the molecular basis of CR has remained obscure. Recently, NAD-dependent Sir2 deacetylases have emerged as key regulators that mediate the adaptive response to CR. Here, we describe the tissue-dependent functions of the mammalian Sir2 ortholog, Sirt1/Sir2α and present a molecular framework in which Sirt1 orchestrates multiple physiological changes into a coordinated response to CR in mammals.

Section editors:Siu Sylvia Lee – Cornell University, Ithaca, USAJavier Apfeld – Harvard Medical School, Boston, USA