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

Authors: Belenky P; Racette FG; Bogan KL; McClure JM; Smith JS; Brenner C

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.

Keywords: Gene Silencing/drug effects; Histone Deacetylases/*metabolism; Metabolic Networks and Pathways; N-Glycosyl Hydrolases/*metabolism; NAD/*metabolism; Niacin/metabolism; Niacinamide/*analogs & derivatives/metabolism/pharmacology; Nicotinamidase/metabolism; Phosphotransferases (Alcohol Group Acceptor)/*metabolism; Purine-Nucleoside Phosphorylase/*metabolism; Saccharomyces cerevisiae/cytology/genetics/*metabolism; Saccharomyces cerevisiae Proteins/*metabolism; Signal Transduction; Silent Information Regulator Proteins, Saccharomyces cerevisiae/*metabolism; Sirtuin 2; Sirtuins/*metabolism
Journal: Cell
Volume: 129
Issue: 3
Pages: 473-84
Date: May 8, 2007
PMID: 17482543
Select reference article to upload


Citation:

Belenky P, Racette FG, Bogan KL, McClure JM, Smith JS, Brenner C (2007) Nicotinamide riboside promotes Sir2 silencing and extends lifespan via Nrk and Urh1/Pnp1/Meu1 pathways to NAD+. Cell 129: 473-84.


Study
Update (Admin) | Auto-Update

Comment on This Data Unit