Sirtuin activators mimic caloric restriction and delay ageing in metazoans

Jason G. Wood, Blanka Rogina, Siva Lavu, Konrad Howitz, Stephen L. Helfand, Marc Tatar and David Sinclair

Department of Pathology, Harvard Medical School, 77 Ave. Louis Pasteur, Boston, Massachusetts 02115, USA
Department of Genetics and Developmental Biology, University of Connecticut Health Center, 263 Farmington Ave., Farmington, Connecticut 06030, USA
BIOMOL Research Laboratories, Inc., 5120 Butler Pike, Plymouth Meeting, Pennsylvania 19462, USA
Department of Ecology and Evolutionary Biology, Box G-W, Brown University, Providence, Rhode Island 02912, USA.

Caloric restriction extends lifespan in numerous species. In the budding yeast Saccharomyces cerevisiae this effect requires Sir2, a member of the sirtuin family of NAD+-dependent deacetylases. Sirtuin activating compounds (STACs) can promote the survival of human cells and extend the replicative lifespan of yeast. Here we show that resveratrol and other STACs activate sirtuins from Caenorhabditis elegans and Drosophila melanogaster, and extend the lifespan of these animals without reducing fecundity. Lifespan extension is dependent on functional Sir2, and is not observed when nutrients are restricted. Together these data indicate that STACs slow metazoan ageing by mechanisms that may be related to caloric restriction.