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Requirement of NAD and SIR2 for Life-Span Extension by Calorie Restriction in Saccharomyces cerevisiae
Abstract
Calorie restriction extends life-span in a wide variety of organisms. Although it has been suggested that calorie restriction may work by reducing the levels of reactive oxygen species produced during respiration, the mechanism by which this regimen slows aging is uncertain. Here, we mimicked calorie restriction in yeast by physiological or genetic means and showed a substantial extension in life-span. This extension was not observed in strains mutant for SIR2 (which encodes the silencing protein Sir2p) or NPT1 (a gene in a pathway in the synthesis of NAD, the oxidized form of nicotinamide adenine dinucleotide). These findings suggest that the increased longevity induced by calorie restriction requires the activation of Sir2p by NAD.
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“The NAD+-dependent deacetylase SIR2 was one of the earliest genes to be implicated in the response to caloric restriction, initially in a yeast model (81).”
From Neural mechanisms of ageing and cognitive decline (2010) · cites this paper as [81]
In the citing paper
“It has been proposed that Sir2 activity ties the energy status of the yeast cell to longevity (Blander and Guarente, 2004; Lin et al., 2000”
From DNA Repair, Genome Stability, and Aging (2005) · cites this paper as Lin et al., 2000
In the citing paper
“an intervention capable of extending life span in many different organisms from yeast to mammals (Cohen et al., 2004; Howitz et al., 2003; Lin et al., 2000; Rogina and Helfand, 2004; Wood et al., 2004”
From DNA Repair, Genome Stability, and Aging (2005) · cites this paper as Lin et al., 2000
In the citing paper
“Indeed, different situations of energy restriction, including fasting and exercise, increase NAD+ levels and trigger SIRT1/PGC-1α-dependent mitochondrial adaptation (Lin et al, 2000; Houtkooper et al, 2012).”
From Mitochondrial response to nutrient availability and its role in metabolic disease (2014) · cites this paper as Lin et al, 2000
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Metadata
- Authors
- Lin, S.-J., Defossez, P.-A., & Guarente, L.
- Affiliations
- Massachusetts Institute of Technology (US)
- Venue
- Science
- Published
- 2000-09-22
- Volume
- 289
- Issue
- 5487
- Pages
- 2126-2128
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1987738803
- Cited by
- 1,775
- References
- 23
- Citations by year
- 2026: 19 · 2025: 19 · 2024: 36 · 2023: 35 · 2022: 38 · 2021: 48 · 2020: 51 · 2019: 50 · 2018: 64 · 2017: 58 · 2016: 67 · 2015: 72 · 2014: 77 · 2013: 92 · 2012: 90
- FWCI
- 18.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5f32ag005857-02)
- National Institute on Aging (5-F32-AG05857-02)
- 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, aging, NAD+, Sir2, Sir2p, Saccharomyces cerevisiae, reactive oxygen species, longevity
- MeSH terms
- Energy Intake, DNA, Circular, DNA, Fungal, DNA, Ribosomal, Enzyme Activation, Glucose, Histone Deacetylases, Longevity, Mutation, NAD, Pentosyltransferases, Recombination, Genetic, Saccharomyces cerevisiae, Trans-Activators, Cyclic AMP-Dependent Protein Kinases, Gene Silencing, Sirtuins, Silent Information Regulator Proteins, Saccharomyces cerevisiae, Sirtuin 2
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