Cited by 1,087Mitochondrial Function and PathologyGenetics, Aging, and Longevity in Model OrganismsAutophagy in Disease and Therapy

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The role of mitochondria in aging

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Bratic, Ana, Larsson, Nils-Göran·2013·Journal of Clinical Investigation

DOI 10.1172/jci64125PMC PMC3582127

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Abstract

Over the last decade, accumulating evidence has suggested a causative link between mitochondrial dysfunction and major phenotypes associated with aging. Somatic mitochondrial DNA (mtDNA) mutations and respiratory chain dysfunction accompany normal aging, but the first direct experimental evidence that increased mtDNA mutation levels contribute to progeroid phenotypes came from the mtDNA mutator mouse. Recent evidence suggests that increases in aging-associated mtDNA mutations are not caused by damage accumulation, but rather are due to clonal expansion of mtDNA replication errors that occur during development. Here we discuss the caveats of the traditional mitochondrial free radical theory of aging and highlight other possible mechanisms, including insulin/IGF-1 signaling (IIS) and the target of rapamycin pathways, that underlie the central role of mitochondria in the aging process.

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Authors: Bratic, A., & Larsson, N.-G.
Affiliations: Max Planck Society (DE)
Corresponding author: Larsson, Nils-Göran
ORCID: Larsson, Nils-Göran
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2013-03-01
Volume: 123
Issue: 3
Pages: 951-957
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci64125
PMC: PMC3582127
OpenAlex: W2112299930
Cited by: 1,087
References: 128
Citations by year: 2026: 68 · 2025: 88 · 2024: 72 · 2023: 82 · 2022: 98 · 2021: 77 · 2020: 102 · 2019: 73 · 2018: 86 · 2017: 76 · 2016: 87 · 2015: 81 · 2014: 66 · 2013: 30
FWCI: 8.27
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
MPG.PuRe (Max Planck Society) (submittedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
Keywords: mitochondria, aging, mitochondrial dysfunction, somatic mtDNA mutations, respiratory chain deficiency, progeroid phenotype, clonal expansion, free radical theory of aging, insulin/IGF-1 signaling, mTOR signaling
MeSH terms: Aging, Animals, DNA, Mitochondrial, Free Radicals, Humans, Mitochondria, Mutation, Signal Transduction, Mutagenesis, Cellular Senescence

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