Sir2-Independent Life Span Extension by Calorie Restriction in Yeast
Open accessAbstract
Calorie restriction slows aging and increases life span in many organisms. In yeast, a mechanistic explanation has been proposed whereby calorie restriction slows aging by activating Sir2. Here we report the identification of a Sir2-independent pathway responsible for a majority of the longevity benefit associated with calorie restriction. Deletion of FOB1 and overexpression of SIR2 have been previously found to increase life span by reducing the levels of toxic rDNA circles in aged mother cells. We find that combining calorie restriction with either of these genetic interventions dramatically enhances longevity, resulting in the longest-lived yeast strain reported thus far. Further, calorie restriction results in a greater life span extension in cells lacking both Sir2 and Fob1 than in cells where Sir2 is present. These findings indicate that Sir2 and calorie restriction act in parallel pathways to promote longevity in yeast and, perhaps, higher eukaryotes.
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Sirtuins' involvement in caloric restriction is debated and depends on context, differing between yeast genetic backgrounds and mouse tissues.
“It is important to note, however, that the potential roles of sirtuins in caloric restriction are controversial and context dependent (see page 480), differing markedly across genetic backgrounds in yeast (85) and tissue types in mice (86).”
From Neural mechanisms of ageing and cognitive decline (2010) · cites this paper as [85]
In yeast, the involvement of Sir2 in caloric restriction appears to be strain specific.
“although in yeast the involvement of Sir2 in CR appears to be strain specific (Kaeberlein et al., 2004”
From DNA Repair, Genome Stability, and Aging (2005) · cites this paper as Kaeberlein et al., 2004
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Self-citation
- Authors
- Kaeberlein, M., Kirkland, K. T., Fields, S., & Kennedy, B. K.
- Affiliations
- University of Washington (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Kennedy, Brian K
- Venue
- PLoS Biology
- Publisher
- Public Library of Science (PLoS)
- Published
- 2004-08-24
- Volume
- 2
- Issue
- 9
- Pages
- e296
- ISSN
- 1544-9173 (ISSN-L)
- 1545-7885
- PMC
- PMC514491
- OpenAlex
- W2006022142
- Cited by
- 441
- References
- 40
- Citations by year
- 2026: 9 · 2025: 6 · 2024: 3 · 2023: 6 · 2022: 9 · 2021: 11 · 2020: 16 · 2019: 18 · 2018: 9 · 2017: 16 · 2016: 19 · 2015: 26 · 2014: 22 · 2013: 29 · 2012: 32
- FWCI
- 9.12
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- Howard Hughes Medical Institute
- American Federation for Aging Research
- University of Washington
- National Institutes of Health (AG013280)
- National Institute on Aging (P30AG013280)
- 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
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- caloric restriction, lifespan extension, Sir2, Fob1, aging, yeast longevity
- MeSH terms
- Culture Media, DNA-Binding Proteins, DNA, Ribosomal, Genetic Techniques, Histone Deacetylases, Models, Biological, Mutation, Phenotype, Plasmids, Saccharomyces cerevisiae, Species Specificity, Time Factors, Gene Expression Regulation, Fungal, Gene Deletion, Saccharomyces cerevisiae Proteins, Databases, Genetic, Caloric Restriction, Sirtuins, Silent Information Regulator Proteins, Saccharomyces cerevisiae, Sirtuin 2
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