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

Genes Dev. 2004 Jan 1;18(1):12-6. doi: 10.1101/gad.1164804.


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.

Publication types

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

MeSH terms

  • Culture Media
  • NAD / metabolism*
  • Oxidation-Reduction
  • Saccharomyces cerevisiae / growth & development*
  • Sirtuins / metabolism


  • Culture Media
  • NAD
  • Sirtuins