Cited by 1,775Genetics, Aging, and Longevity in Model OrganismsSirtuins and Resveratrol in MedicineFungal and yeast genetics research

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Requirement of NAD and SIR2 for Life-Span Extension by Calorie Restriction in Saccharomyces cerevisiae

Lin, Su-Ju, Defossez, Pierre-Antoine, Guarente, Leonard·2000·Science

DOI 10.1126/science.289.5487.2126

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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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Authors: Lin, S.-J., Defossez, P.-A., & Guarente, L.
Affiliations: Massachusetts Institute of Technology (US)
ORCID: Lin, Su-Ju
Defossez, Pierre-Antoine
Guarente, Leonard
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2000-09-22
Volume: 289
Issue: 5487
Pages: 2126-2128
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.289.5487.2126
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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Requirement of NAD and SIR2 for Life-Span Extension by Calorie Restriction in Saccharomyces cerevisiae

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