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The role of mitochondria in aging
Open accessAbstract
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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In the citing paper
“accumulation of such damages occurs during aging [66].”
From Repair of Oxidative DNA Damage, Cell-Cycle Regulation and Neuronal Death May Influence the Clinical Manifestation of Alzheimer’s Disease (2014) · cites this paper as [66]
In the citing paper
“Mitochondrial function declines with aging in model organisms and humans (58).”
From Connecting aging biology and inflammation in the omics era (2022) · cites this paper as [58]
In the citing paper
“A progressive mitochondrial dysfunction is known to occur with age (31)(32)(33).”
From Human Aging and Longevity Are Characterized by High Levels of Mitokines (2019) · cites this paper as [33]
In the citing paper
“A direct relationship between mitochondrial dysfunction and aging has been suggested by many studies (for review, see ref. 93)”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [93]
In the citing paper
“secondary alterations in mitochondrial function driven by age-related cellular and metabolic changes may also contribute to the aging process93.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [93]
In the citing paper
“Defective mitophagy has also been linked with premature aging and many age-associated disorders, such as Alzheimer’s and Parkinson’s diseases (25–28).”
From Impaired mitophagy leads to cigarette smoke stress‐induced cellular senescence: implications for chronic obstructive pulmonary disease (2015) · cites this paper as [26]
In the citing paper
“Previous studies have reported diminished expressions of mitochondrial respiratory complex subunits, mitochondrial respiration, and ATP levels in skeletal muscle [66].”
From Exerkines and Sarcopenia: Unveiling the Mechanism Behind Exercise-Induced Mitochondrial Homeostasis (2025) · cites this paper as [66]
In the citing paper
“Mitochondrial function declines with age due either to ROS and/or an accumulation of mutations in mitochondrial DNA (151).”
From A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan (2021) · cites this paper as [151]
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Metadata
- 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
- Published
- 2013-03-01
- Volume
- 123
- Issue
- 3
- Pages
- 951-957
- ISSN
- 0021-9738 (ISSN-L)
- 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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