Nicotinamide riboside promotes Sir2 silencing and extends lifespan via Nrk and Urh1/Pnp1/Meu1 pathways to NAD

Peter Belenky; Frances G Racette; Katrina L Bogan; Julie M McClure; Jeffrey S Smith; Charles Brenner

doi:10.1016/j.cell.2007.03.024

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Nicotinamide riboside promotes Sir2 silencing and extends lifespan via Nrk and Urh1/Pnp1/Meu1 pathways to NAD

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Nicotinamide riboside promotes Sir2 silencing and extends lifespan via Nrk and Urh1/Pnp1/Meu1 pathways to NAD

Peter Belenky, Frances G Racette, Katrina L Bogan, Julie M McClure, Jeffrey S Smith and Charles Brenner

Cell, Vol.129(3), pp.473-484

05/04/2007

DOI: 10.1016/j.cell.2007.03.024

PMID: 17482543

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Abstract

Although NAD(+) biosynthesis is required for Sir2 functions and replicative lifespan in yeast, alterations in NAD(+) precursors have been reported to accelerate aging but not to extend lifespan. In eukaryotes, nicotinamide riboside is a newly discovered NAD(+) precursor that is converted to nicotinamide mononucleotide by specific nicotinamide riboside kinases, Nrk1 and Nrk2. In this study, we discovered that exogenous nicotinamide riboside promotes Sir2-dependent repression of recombination, improves gene silencing, and extends lifespan without calorie restriction. The mechanism of action of nicotinamide riboside is totally dependent on increased net NAD(+) synthesis through two pathways, the Nrk1 pathway and the Urh1/Pnp1/Meu1 pathway, which is Nrk1 independent. Additionally, the two nicotinamide riboside salvage pathways contribute to NAD(+) metabolism in the absence of nicotinamide-riboside supplementation. Thus, like calorie restriction in the mouse, nicotinamide riboside elevates NAD(+) and increases Sir2 function.

Signal Transduction

Niacinamide - analogs & derivatives

Gene Silencing - drug effects

Niacinamide - metabolism

Nicotinamidase - metabolism

Silent Information Regulator Proteins, Saccharomyces cerevisiae - metabolism

Saccharomyces cerevisiae - genetics

Histone Deacetylases - metabolism

N-Glycosyl Hydrolases - metabolism

Niacin - metabolism

Phosphotransferases (Alcohol Group Acceptor) - metabolism

Saccharomyces cerevisiae - cytology

Saccharomyces cerevisiae - metabolism

Sirtuin 2

Metabolic Networks and Pathways

Saccharomyces cerevisiae Proteins - metabolism

Niacinamide - pharmacology

Purine-Nucleoside Phosphorylase - metabolism

Sirtuins - metabolism

NAD - metabolism

Details

Title: Subtitle: Nicotinamide riboside promotes Sir2 silencing and extends lifespan via Nrk and Urh1/Pnp1/Meu1 pathways to NAD
Creators: Peter Belenky - Departments of Genetics and Biochemistry and the Norris Cotton Cancer Center, Dartmouth Medical School, Rubin 733-HB7937, Lebanon, NH 03756, USA
Frances G Racette
Katrina L Bogan
Julie M McClure
Jeffrey S Smith
Charles Brenner
Resource Type: Journal article
Publication Details: Cell, Vol.129(3), pp.473-484
DOI: 10.1016/j.cell.2007.03.024
PMID: 17482543
NLM abbreviation: Cell
ISSN: 0092-8674
eISSN: 1097-4172
Publisher: United States
Grant note: GM75240 / NIGMS NIH HHS T32 GM008136 / NIGMS NIH HHS
Language: English
Date published: 05/04/2007
Academic Unit: Biochemistry and Molecular Biology; Internal Medicine
Record Identifier: 9983788432802771

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