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

The role of mitochondria in aging

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

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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  1. Orr WC, Sohal RS. Extension of life-span by over- expression of superoxide dismutase and cata- lase in Droso phila melanogaster. Science. 1994; 263(5150):1128-1130.

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Authors
Bratic, A., & Larsson, N.-G.
Affiliations
Max Planck Society (DE)
Corresponding author
Larsson, Nils-Göran
Venue
Journal of Clinical Investigation
Published
2013-03-01
Volume
123
Issue
3
Pages
951-957
ISSN
0021-9738 (ISSN-L)
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
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
  • Health Sciences › Medicine › Epidemiology › 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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