Nicotinamide Riboside Promotes Sir2 Silencing and Extends Lifespan via Nrk and Urh1/Pnp1/Meu1 Pathways to NAD+
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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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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.”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [189]
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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
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 2269 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- 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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