Calorie restriction extends yeast life span by lowering the level of NADH
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Calorie restriction (CR) extends life span in a wide variety of species. Previously, we showed that calorie restriction increases the replicative life span in yeast by activating Sir2, a highly conserved NAD-dependent deacetylase. Here we test whether CR activates Sir2 by increasing the NAD/NADH ratio or by regulating the level of nicotinamide, a known inhibitor of Sir2. We show that CR decreases NADH levels, and that NADH is a competitive inhibitor of Sir2. A genetic intervention that specifically decreases NADH levels increases life span, validating the model that NADH regulates yeast longevity in response to CR.
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Sirtuin activity requires NAD+ as a cofactor, and the cellular redox status-based NAD+/NADH ratio can affect sirtuins at the transcriptional or post-transcriptional level.
“As sirtuin activity requires NAD+ as a cofactor, cellular redox status-based NAD+/NADH ratio can further affect sirtuins [188] at the transcriptional or post-transcriptional level of activity [189], [190].”
From Redox control of senescence and age-related disease. (2017) · cites this paper as [188]
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- Authors
- Lin, S.-J., Ford, E., Haigis, M., Liszt, G., & Guarente, L.
- Affiliations
- Massachusetts Institute of Technology (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2004-01-01
- Volume
- 18
- Issue
- 1
- Pages
- 12-16
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC314267
- OpenAlex
- W2136829516
- Cited by
- 632
- References
- 31
- Citations by year
- 2026: 8 · 2025: 6 · 2024: 11 · 2023: 11 · 2022: 8 · 2021: 25 · 2020: 20 · 2019: 17 · 2018: 34 · 2017: 20 · 2016: 32 · 2015: 33 · 2014: 35 · 2013: 36 · 2012: 36
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ellison Medical Foundation
- National Institutes of Health
- 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, replicative lifespan, Sir2, NADH, NAD+/NADH ratio, nicotinamide, NAD+-dependent deacetylase, yeast longevity, competitive inhibition
- MeSH terms
- Culture Media, NAD, Oxidation-Reduction, Saccharomyces cerevisiae, Sirtuins
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