Mitochondria—A Nexus for Aging, Calorie Restriction, and Sirtuins?
Open accessAbstract
Recent studies of calorie restriction in several organisms demonstrate an increase in mitochondrial activity that is associated with the salutary effects of this dietary restriction regimen. In this Essay, I speculate on how an increase in mitochondrial activity might provide benefit and discuss how diet, mitochondria, and sirtuins might interact in a pathway to slow aging and associated diseases.
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Aged tissues accumulate mitochondrial DNA mutations that cause respiratory chain deficiency and increased reactive oxygen species.
“Aged tissues show accumulation of mitochondrial DNA (mtDNA) mutations causing respiratory chain deficiency and increased reactive oxygen species (ROS)2,4”
From Telomere dysfunction induces metabolic and mitochondrial compromise (2011) · cites this paper as [4]
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 [65]
No impact of CR on mitochondrial density could be evidenced in the present study.
“Although CR has been proposed to increase mitochondrial content (Guarente, 2008), no impact of CR on mitochondrial density could be evidenced in the present study.”
From Effects of Aging and Caloric Restriction on Fiber Type Composition, Mitochondrial Morphology and Dynamics in Rat Oxidative and Glycolytic Muscles (2019) · cites this paper as Guarente, 2008
Calorie restriction favors mitochondrial biogenesis, oxygen use and ATP formation, and expression of SIRT1, which activates PGC1-α.
“How this is related to mitochondrial function is not clear, but evidence suggests that calorie restriction favors mitochondrial biogenesis, oxygen use and ATP formation, and expression of SIRT1, which activates PGC1-α (121, 203).”
From Mitochondrial Dysfunction in Diabetes: From Molecular Mechanisms to Functional Significance and Therapeutic Opportunities (2010) · cites this paper as [121]
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- Authors
- Guarente, L.
- Affiliations
- Massachusetts Institute of Technology (US)
- Corresponding author
- Guarente, Leonard
- ORCID
- Guarente, Leonard
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2008-01
- Volume
- 132
- Issue
- 2
- Pages
- 171-176
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC2680180
- OpenAlex
- W2066762257
- Cited by
- 513
- References
- 46
- Citations by year
- 2026: 5 · 2025: 14 · 2024: 10 · 2023: 11 · 2022: 13 · 2021: 20 · 2020: 28 · 2019: 20 · 2018: 24 · 2017: 17 · 2016: 22 · 2015: 22 · 2014: 46 · 2013: 46 · 2012: 42
- FWCI
- 4.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 2024 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- mitochondria, caloric restriction, sirtuins, aging, dietary restriction, mitochondrial activity, age-related diseases
- MeSH terms
- Aging, Animals, Humans, Mitochondria, Models, Biological, Caloric Restriction, Sirtuins
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