Cited by 411Sirtuins and Resveratrol in MedicineGenetics, Aging, and Longevity in Model OrganismsBiochemical and Molecular Research

Nicotinamide Riboside Promotes Sir2 Silencing and Extends Lifespan via Nrk and Urh1/Pnp1/Meu1 Pathways to NAD+

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Belenky, Peter, Racette, Frances G., Bogan, Katrina L., McClure, Julie M., Smith, Jeffrey S., Brenner, Charles·2007·Cell

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.

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Crossref · 10.1016/j.cell.2007.03.024

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  • In wild-type yeast and C. elegans, low micromolar concentrations of NR extend lifespan in a sirtuin-dependent manner.

    “In both wild-type yeast and C. elegans, low (micromolar) concentrations of NR extend lifespan in a sirtuin-dependent manner135,189,190.”

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Authors
Belenky, P., Racette, F. G., Bogan, K. L., McClure, J. M., Smith, J. S., & Brenner, C.
Affiliations
  • Dartmouth College (US)
  • University of Virginia Health System (US)
Corresponding author
  • Smith, Jeffrey S.
  • Brenner, Charles
Venue
Cell
Publisher
Elsevier BV
Published
2007-05
Volume
129
Issue
3
Pages
473-484
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2168486424
Cited by
411
References
68
Citations by year
2026: 13 · 2025: 15 · 2024: 19 · 2023: 26 · 2022: 38 · 2021: 19 · 2020: 35 · 2019: 23 · 2018: 30 · 2017: 22 · 2016: 16 · 2015: 17 · 2014: 22 · 2013: 17 · 2012: 15
FWCI
10.50
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of General Medical Sciences (GM75240, R01GM075240, T32GM008136)
Topics
  • Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
Keywords
nicotinamide riboside, Sir2, replicative lifespan, NAD biosynthesis, gene silencing, NAD+ salvage pathway, caloric restriction, aging, Saccharomyces cerevisiae
MeSH terms
Histone Deacetylases, NAD, Niacin, Nicotinamidase, Niacinamide, N-Glycosyl Hydrolases, Purine-Nucleoside Phosphorylase, Pyridinium Compounds, Saccharomyces cerevisiae, Signal Transduction, Phosphotransferases (Alcohol Group Acceptor), Gene Silencing, Saccharomyces cerevisiae Proteins, Sirtuins, Silent Information Regulator Proteins, Saccharomyces cerevisiae, Metabolic Networks and Pathways, Sirtuin 2

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