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Genes Dev. 2004 Jan 1;18(1):12-6.

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

Author information

  • 1Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. slin@ucdavis.edu

Abstract

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.

PMID:
14724176
[PubMed - indexed for MEDLINE]
PMCID:
PMC314267
Free PMC Article

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