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Mitochondrial DNA mutations and aging: devils in the details?
Open accessAbstract
Although several lines of evidence support a role for accumulating somatic mitochondrial DNA (mtDNA) mutations in the etiology of aging, it remains unclear if they are a major cause of age-related deterioration and death. Mouse models that harbor elevated mtDNA mutation frequencies age prematurely; these findings were thought to provide conclusive evidence for a causal role of such mutations in aging. Yet, the presence of several conflicting reports has sparked controversy in the field and this is further aggravated by discrepancies in the estimates of mtDNA mutant fractions, which disagree by orders of magnitude. Here, we briefly review the evidence and some of the unresolved questions surrounding a causative role for accumulating mtDNA mutations in aging.
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“Our data from POLGD257A mice indicate that MiDAS can occur in vivo, although mtDNA mutations accumulate with age at rates well below that seen in POLGD257A mice (Khrapko and Vijg, 2009).”
From Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype (2016) · cites this paper as Khrapko and Vijg, 2009
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“Mitochondrial dysfunction has been linked to aging (Khrapko and Vijg, 2009), but it is not clear how it drives aging, particularly in mitotic tissues.”
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Metadata
- Authors
- Khrapko, K., & Vijg, J.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Albert Einstein College of Medicine (US)
- Corresponding author
- Khrapko, Konstantin
- Vijg, Jan
- Venue
- Trends in Genetics
- Publisher
- Elsevier BV
- Published
- 2009-02
- Volume
- 25
- Issue
- 2
- Pages
- 91-98
- ISSN
- 0168-9525 (ISSN-L)
- PMC
- PMC2811092
- OpenAlex
- W1996511649
- Cited by
- 112
- References
- 68
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 1 · 2022: 3 · 2021: 4 · 2020: 5 · 2019: 8 · 2018: 6 · 2017: 10 · 2016: 5 · 2015: 6 · 2014: 12 · 2013: 13 · 2012: 5
- FWCI
- 0.69
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Trends in Genetics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Ellison Medical Foundation
- United Mitochondrial Disease Foundation
- National Institutes of Health
- National Institute on Aging (AG 17242, R01AG020438, AG 20438, P01AG017242, AG19787, R01AG019787)
- National Institute of Neurological Disorders and Stroke (NS058988, R01NS058988)
- 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 › Telomeres, Telomerase, and Senescence
- Keywords
- mitochondrial DNA mutations, aging, premature aging, mouse model
- MeSH terms
- Aging, Animals, DNA, Mitochondrial, Humans, Mutation, Oxidation-Reduction, Phenotype, Phosphorylation, Stem Cells, Substantia Nigra, Cellular Senescence, Muscle, Skeletal, Mice
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