Tissue-specific regulation of SIRT1 by calorie restriction
Open accessAbstract
Calorie restriction (CR) has been reported to increase SIRT1 protein levels in mice, rats, and humans, and elevated activity of SIRT1 orthologs extends life span in yeast, worms, and flies. In this study, we challenge the paradigm that CR induces SIRT1 activity in all tissues by showing that activity of this sirtuin in the liver is, in fact, reduced by CR and activated by a high-caloric diet. We demonstrate this change both by assaying levels of SIRT1 and its small molecule regulators, NAD and NADH, as well as assessing phenotypes of a liver-specific SIRT1 knockout mouse on various diets. Our findings suggest that designing CR mimetics that target SIRT1 to provide uniform systemic benefits may be more complex than currently imagined.
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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 [86]
Sirtuins are implicated in CR-mediated lifespan extension, and SIRT1 is regulated by CR in mice in a tissue-specific manner.
“Sirtuins have been implicated in the mechanism of lifespan extension by CR [65] and SIRT1 is regulated by CR in mice in a tissue specific manner [66].”
From PGC-1α in aging and anti-aging interventions (2009) · cites this paper as [66]
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1 retracted
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- Authors
- Chen, D., Bruno, J., Easlon, E., Lin, S.-J., Cheng, H.-L., Alt, F. W., & Guarente, L.
- Affiliations
- Massachusetts Institute of Technology (US)
- University of California, Davis (US)
- Howard Hughes Medical Institute (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2008-06-11
- Volume
- 22
- Issue
- 13
- Pages
- 1753-1757
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC2492662
- OpenAlex
- W2097487849
- Cited by
- 567
- References
- 28
- Citations by year
- 2026: 10 · 2025: 13 · 2024: 13 · 2023: 13 · 2022: 14 · 2021: 30 · 2020: 36 · 2019: 29 · 2018: 29 · 2017: 27 · 2016: 33 · 2015: 39 · 2014: 33 · 2013: 48 · 2012: 45
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Glenn Foundation for Medical Research
- Leukemia and Lymphoma Society
- National Institutes of Health
- National Institute on Aging (R56AG015339, AG15339-09, R01AG015339, R01AG011119)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- SIRT1, caloric restriction, tissue-specific gene regulation, liver, sirtuins, NAD+, NADH, hypercaloric diet, aging, longevity
- MeSH terms
- Animals, Gene Expression Regulation, Liver, Longevity, NAD, Organ Specificity, Mice, Knockout, Muscle, Skeletal, Caloric Restriction, Sirtuins, Mice, Adipose Tissue, White, Sirtuin 1
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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