Do mtDNA deletions drive premature aging in mtDNA mutator mice?
Open accessAbstract
Deletions in mitochondrial DNA (mtDNA) have long been suspected to be involved in mammalian aging, but their role remains controversial. Recent research has demonstrated that relatively higher levels of mtDNA deletions correlate with premature aging in mtDNA mutator mice, which led to the conclusion that premature aging in these mice is driven by mtDNA deletions. However, it is reported here that the absolute level of deletions in mutator mice is quite low, especially when compared with the level of point mutations in these mice. It is thus argued that the available data are insufficient to conclude that mtDNA mutations drive premature aging in mtDNA mutator mice. It remains possible that clonal expansion of mtDNA deletions may result in sufficiently high levels to play a role in age-related dysfunction in some cells, but assessing this possibility will require studies of the distribution of these deletions among different cell types and in individual cells.
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The overall fraction of deletions in tissues from the mtDNA mutator mouse was only measured to be ~1.0%.
“In fact, the overall fraction of deletions in tissues from the mtDNA mutator mouse was only measured to be ~1.0% (Kraytsberg et al., 2009).”
From Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases (2017) · cites this paper as Kraytsberg et al., 2009
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- Authors
- Kraytsberg, Y., Simon, D. K., Turnbull, D. M., & Khrapko, K.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Khrapko, Konstantin
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2009-07-21
- Volume
- 8
- Issue
- 4
- Pages
- 502-506
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- PMC
- PMC3137638
- OpenAlex
- W2044099701
- Cited by
- 42
- References
- 22
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 1 · 2021: 2 · 2019: 1 · 2018: 1 · 2016: 4 · 2015: 4 · 2014: 7 · 2013: 3
- FWCI
- 2.28
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Aging Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- Medical Research Council (G0700718)
- National Institute on Aging (R03AG035223, R01AG019787)
- National Institute of Mental Health (R01MH085801)
- National Institute of Neurological Disorders and Stroke (R01NS058988, R03NS053840)
- 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 › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- mitochondrial DNA deletions, premature aging, mitochondrial DNA mutations, point mutations, clonal expansion, mitochondrial dysfunction
- MeSH terms
- DNA Polymerase gamma, Animals, Brain, DNA-Directed DNA Polymerase, DNA, Mitochondrial, Mice, Transgenic, Mutation, Phenotype, Gene Deletion, Aging, Premature, Mice
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