The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
Nicotinamide and PNC1 govern lifespan extension by calorie restriction in Saccharomyces cerevisiae
Open accessAbstract
Calorie restriction extends lifespan in a broad range of organisms, from yeasts to mammals. Numerous hypotheses have been proposed to explain this phenomenon, including decreased oxidative damage and altered energy metabolism. In Saccharomyces cerevisiae, lifespan extension by calorie restriction requires the NAD+-dependent histone deacetylase, Sir2 (ref. 1). We have recently shown that Sir2 and its closest human homologue SIRT1, a p53 deacetylase, are strongly inhibited by the vitamin B3 precursor nicotinamide. Here we show that increased expression of PNC1 (pyrazinamidase/nicotinamidase 1), which encodes an enzyme that deaminates nicotinamide, is both necessary and sufficient for lifespan extension by calorie restriction and low-intensity stress. We also identify PNC1 as a longevity gene that is responsive to all stimuli that extend lifespan. We provide evidence that nicotinamide depletion is sufficient to activate Sir2 and that this is the mechanism by which PNC1 regulates longevity. We conclude that yeast lifespan extension by calorie restriction is the consequence of an active cellular response to a low-intensity stress and speculate that nicotinamide might regulate critical cellular processes in higher organisms.
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“Several studies highlight how the external environment and the genetic background of an organism have pivotal roles in the aging process by affecting events that maintain epigenetic information 2,3 .”
From Mechanisms, pathways and strategies for rejuvenation through epigenetic reprogramming (2023) · cites this paper as [3]
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“NAM, in contrast, is a well reported and widely used sirtuin inhibitor31 and has been recently shown to inhibit NAD+-consuming activities in vivo24.”
From NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells (2016) · cites this paper as [31]
In the citing paper
“In response to calorie restriction, the yeast NAD biosynthetic gene that catalyses the first and rate-limiting step in NAD+ biosynthesis, PNC1, is induced46.”
From Mitochondrial and metabolic dysfunction in ageing and age-related diseases (2022) · cites this paper as [46]
In the citing paper
“The resulting availability of NAD+ increases SIR2 activity, which boosts mitochondrial respiration and suppresses recombinant DNA recombination11,46, a known cause of ageing in yeast47.”
From Mitochondrial and metabolic dysfunction in ageing and age-related diseases (2022) · cites this paper as [46]
In the citing paper
“The upregulation of the NAD salvage pathway, which recycles NAD+ from nicotinamide, was first shown to extend lifespan and mimic caloric restriction in yeast cells46.”
From Mitochondrial and metabolic dysfunction in ageing and age-related diseases (2022) · cites this paper as [46]
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Calorie restriction extends Saccharomyces cerevisiae lifespan by increasing respiration
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Metadata
- Authors
- Anderson, R. M., Bitterman, K. J., Wood, J. G., Medvedik, O., & Sinclair, D. A.
- Affiliations
- Harvard University (US)
- Corresponding author
- Sinclair, David A.
- Venue
- Nature
- Published
- 2003-05
- Volume
- 423
- Issue
- 6936
- Pages
- 181-185
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4802858
- OpenAlex
- W2006806054
- Cited by
- 736
- References
- 30
- Citations by year
- 2026: 18 · 2025: 17 · 2024: 11 · 2023: 10 · 2022: 26 · 2021: 18 · 2020: 24 · 2019: 23 · 2018: 30 · 2017: 26 · 2016: 29 · 2015: 35 · 2014: 30 · 2013: 24 · 2012: 39
- FWCI
- 13.20
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institute on Aging (R37AG028730, P01AG027916, R01AG028730, R01AG019719, R01AG019972)
- National Institute of General Medical Sciences (R01GM068072)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Keywords
- caloric restriction, lifespan extension, nicotinamide, Sir2, SIRT1, NAD+-dependent histone deacetylase, longevity genes, Saccharomyces cerevisiae, aging
- MeSH terms
- Cell Nucleus, Cytoplasm, Energy Metabolism, Histone Deacetylases, Longevity, NAD, Niacin, Nicotinamidase, Niacinamide, Saccharomyces cerevisiae, Gene Expression Regulation, Fungal, Heat-Shock Response, Gene Silencing, Saccharomyces cerevisiae Proteins, Caloric Restriction, Sirtuins, Silent Information Regulator Proteins, Saccharomyces cerevisiae, Sirtuin 2
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