Sirtuin activators mimic caloric restriction and delay ageing in metazoans

Nature. 2004 Aug 5;430(7000):686-9. doi: 10.1038/nature02789. Epub 2004 Jul 14.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aging / drug effects
  • Aging / physiology*
  • Alleles
  • Animal Feed
  • Animals
  • Caenorhabditis elegans / drug effects
  • Caenorhabditis elegans / physiology*
  • Caloric Restriction*
  • Drosophila melanogaster / drug effects
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / physiology*
  • Feeding Behavior / drug effects
  • Feeding Behavior / physiology
  • Female
  • Fertility / drug effects
  • Fertility / physiology
  • Flavonoids / pharmacology
  • Genotype
  • Longevity / drug effects
  • Longevity / physiology*
  • Male
  • Mutation / genetics
  • Phenols / pharmacology
  • Polyphenols
  • Resveratrol
  • Sirtuins / agonists*
  • Sirtuins / metabolism
  • Stilbenes / pharmacology
  • Survival Rate
  • Time Factors

Substances

  • Flavonoids
  • Phenols
  • Polyphenols
  • Stilbenes
  • Sirtuins
  • fisetin
  • Resveratrol