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

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

doi:10.1101/gad.1164804

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

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

Microbiology

Research output: Contribution to journal › Article › peer-review

513 Scopus citations

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.

Original language	English (US)
Pages (from-to)	12-16
Number of pages	5
Journal	Genes and Development
Volume	18
Issue number	1
DOIs	https://doi.org/10.1101/gad.1164804
State	Published - Jan 1 2004

Keywords

Calorie restriction
Longevity regulation
Metabolic signaling

ASJC Scopus subject areas

Genetics
Developmental Biology

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

Abstract

Keywords

ASJC Scopus subject areas

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