Calorie restriction extends yeast life span by lowering the level of NADH

Su Ju Lin, Ethan Ford, Marcia Haigis, Greg Liszt, Leonard Guarente

Research output: Contribution to journalArticlepeer-review

536 Scopus citations


Calorie restriction (CR) extends life span in a wide variety of species. Previously, we showed that calorie restriction increases the replicative life span in yeast by activating Sir2, a highly conserved NAD-dependent deacetylase. Here we test whether CR activates Sir2 by increasing the NAD/NADH ratio or by regulating the level of nicotinamide, a known inhibitor of Sir2. We show that CR decreases NADH levels, and that NADH is a competitive inhibitor of Sir2. A genetic intervention that specifically decreases NADH levels increases life span, validating the model that NADH regulates yeast longevity in response to CR.

Original languageEnglish (US)
Pages (from-to)12-16
Number of pages5
JournalGenes and Development
Issue number1
StatePublished - Jan 1 2004


  • Calorie restriction
  • Longevity regulation
  • Metabolic signaling

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology


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