Calorie restriction extends yeast life span by lowering the level of NADH
SJ Lin, E Ford, M Haigis, G Liszt… - Genes & …, 2004 - genesdev.cshlp.org
SJ Lin, E Ford, M Haigis, G Liszt, L Guarente
Genes & development, 2004•genesdev.cshlp.orgCalorie 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 …
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 …
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.
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