Sirtuin activators mimic caloric restriction and delay ageing in metazoans.
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.
Wood
Jason G
JG
Department of Pathology, Harvard Medical School, 77 Ave. Louis Pasteur, Boston, Massachusetts 02115, USA.
Rogina
Blanka
B
Lavu
Siva
S
Howitz
Konrad
K
Helfand
Stephen L
SL
Tatar
Marc
M
Sinclair
David
D
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
D005419:Flavonoids; D044948:Flavonols; D010636:Phenols; D059808:Polyphenols; D013267:Stilbenes; D037761:Sirtuins; C017875:fisetin; D000077185:Resveratrol