title: Sirtuin activators mimic caloric restriction and delay ageing in metazoans.
abstract: 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 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.
authors.affiliation: Department of Pathology, Harvard Medical School, 77 Ave. Louis Pasteur, Boston, Massachusetts 02115, USA.
authors.forename: Jason G
authors.initials: JG
authors.lastname: Wood
authors.forename: Blanka
authors.initials: B
authors.lastname: Rogina
authors.forename: Siva
authors.initials: S
authors.lastname: Lavu
authors.forename: Konrad
authors.initials: K
authors.lastname: Howitz
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Helfand
authors.forename: Marc
authors.initials: M
authors.lastname: Tatar
authors.forename: David
authors.initials: D
authors.lastname: Sinclair
mesh_terms: D000375:Aging / Q000187:drug effects / Q000502:physiology*; D000483:Alleles; D000821:Animal Feed; D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000502:physiology*; D031204:Caloric Restriction; D004331:Drosophila melanogaster / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology; D005260:Female; D005298:Fertility / Q000187:drug effects / Q000502:physiology; D005419:Flavonoids / Q000494:pharmacology; D044948:Flavonols; D005838:Genotype; D008136:Longevity / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009154:Mutation / Q000235:genetics; D010636:Phenols / Q000494:pharmacology; D059808:Polyphenols; D000077185:Resveratrol; D037761:Sirtuins / Q000819:agonists* / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology; D015996:Survival Rate; D013997:Time Factors
chemical_list: D005419:Flavonoids; D044948:Flavonols; D010636:Phenols; D059808:Polyphenols; D013267:Stilbenes; D037761:Sirtuins; C017875:fisetin; D000077185:Resveratrol