Yeast life-span extension by calorie restriction is independent of NAD fluctuation

Science. 2003 Dec 19;302(5653):2124-2126. doi: 10.1126/science.1088697. Epub 2003 Nov 6.

Abstract

Calorie restriction (CR) slows aging in numerous species. In the yeast Saccharomyces cerevisiae, this effect requires Sir2, a conserved NAD+-dependent deacetylase. We report that CR reduces nuclear NAD+ levels in vivo. Moreover, the activity of Sir2 and its human homologue SIRT1 are not affected by physiological alterations in the NAD+:NADH ratio. These data implicate alternate mechanisms of Sir2 regulation by CR.

MeSH terms

  • Acetaldehyde / metabolism
  • Aerobiosis
  • Bacterial Proteins*
  • CCAAT-Binding Factor / genetics
  • CCAAT-Binding Factor / metabolism
  • Caloric Restriction
  • Culture Media
  • DNA-Binding Proteins
  • Genes, Fungal
  • Genes, Reporter
  • Histidine / metabolism
  • Histone Deacetylases / metabolism*
  • Hydro-Lyases / genetics
  • Hydro-Lyases / metabolism
  • Longevity
  • Magnetic Resonance Spectroscopy
  • NAD / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / physiology*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae / metabolism*
  • Sirtuin 1
  • Sirtuin 2
  • Sirtuins / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Bacterial Proteins
  • CCAAT-Binding Factor
  • Culture Media
  • DNA-Binding Proteins
  • GAL4 protein, S cerevisiae
  • HAP4 protein, S cerevisiae
  • NadR protein, bacteria
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • Saccharomyces cerevisiae Proteins
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae
  • Transcription Factors
  • NAD
  • Histidine
  • SIR2 protein, S cerevisiae
  • SIRT1 protein, human
  • Sirtuin 1
  • Sirtuin 2
  • Sirtuins
  • Histone Deacetylases
  • Hydro-Lyases
  • imidazoleglycerolphosphate dehydratase
  • Acetaldehyde