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Yeast life-span extension by calorie restriction is independent of NAD fluctuation.

ABSTRACT: Calorie restriction (CR) slows aging in numerous species. In the yeast Saccharomyces cerevisiae, this effect requires Sir2, a conserved NAD+-dependent deacetylase. We report that CR reduces nuclear NAD+ levels in vivo. Moreover, the activity of Sir2 and its human homologue SIRT1 are not affected by physiological alterations in the NAD+:NADH ratio. These data implicate alternate mechanisms of Sir2 regulation by CR.

SUBMITTER: Anderson RM

PROVIDER: S-EPMC4998187 | biostudies-literature | 2003 Dec

REPOSITORIES: biostudies-literature

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Yeast life-span extension by calorie restriction is independent of NAD fluctuation.

Anderson Rozalyn M RM Latorre-Esteves Magda M Neves Ana Rute AR Lavu Siva S Medvedik Oliver O Taylor Christopher C Howitz Konrad T KT Santos Helena H Sinclair David A DA

Science (New York, N.Y.) 20031106 5653

Calorie restriction (CR) slows aging in numerous species. In the yeast Saccharomyces cerevisiae, this effect requires Sir2, a conserved NAD+-dependent deacetylase. We report that CR reduces nuclear NAD+ levels in vivo. Moreover, the activity of Sir2 and its human homologue SIRT1 are not affected by physiological alterations in the NAD+:NADH ratio. These data implicate alternate mechanisms of Sir2 regulation by CR. ...[more]

PMID: 14605207

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Sir2-independent life span extension by calorie restriction in yeast.

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Calorie restriction-mediated replicative lifespan extension in yeast is non-cell autonomous.

Project description:In laboratory yeast strains with Sir2 and Fob1 function, wild-type NAD+ salvage is required for calorie restriction (CR) to extend replicative lifespan. CR does not significantly alter steady state levels of intracellular NAD+ metabolites. However, levels of Sir2 and Pnc1, two enzymes that sequentially convert NAD+ to nicotinic acid (NA), are up-regulated during CR. To test whether factors such as NA might be exported by glucose-restricted mother cells to survive later generations, we developed a replicative longevity paradigm in which mother cells are moved after 15 generations on defined media. The experiment reveals that CR mother cells lose the longevity benefit of CR when evacuated from their local environment to fresh CR media. Addition of NA or nicotinamide riboside (NR) allows a moved mother to maintain replicative longevity despite the move. Moreover, conditioned medium from CR-treated cells transmits the longevity benefit of CR to moved mother cells. Evidence suggests the existence of a longevity factor that is dialyzable but is neither NA nor NR, and indicates that Sir2 is not required for the longevity factor to be produced or to act. Data indicate that the benefit of glucose-restriction is transmitted from cell to cell in budding yeast, suggesting that glucose restriction may benefit neighboring cells and not only an individual cell.

| S-EPMC4310591 | biostudies-other

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