Letters to Nature

Nature 430, 686-689 (5 August 2004) | doi:10.1038/nature02789; Received 13 April 2004; Accepted 28 June 2004; Published online 14 July 2004

Sirtuin activators mimic caloric restriction and delay ageing in metazoans

Jason G. Wood1,5, Blanka Rogina2,5, Siva Lavu1, Konrad Howitz3, Stephen L. Helfand2, Marc Tatar4 & David Sinclair1

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

Correspondence to: Marc Tatar4David Sinclair1 Email: david_sinclair@hms.harvard.edu
Email: shelfand@neuron.uchc.edu
Email: marc_tatar@brown.edu

Caloric restriction extends lifespan in numerous species. In the budding yeast Saccharomyces cerevisiae this effect requires Sir2 (ref. 1), a member of the sirtuin family of NAD+-dependent deacetylases2, 3. Sirtuin activating compounds (STACs) can promote the survival of human cells and extend the replicative lifespan of yeast4. 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.


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