The relationship between the aging- and photo-dependent T414G mitochondrial DNA mutation with cellular senescence and reactive oxygen species production in cultured skin fibroblasts
Open accessAbstract
Mutations in the mitochondrial genome (mtDNA) are thought to be one of the causes of age-dependent cellular decline through their detrimental effects on respiration or reactive oxygen species (ROS) production. However, for many mutations, this link has not been clearly established. This study aimed to further investigate the phenotypic importance of a T414G mutation within the control region of mtDNA, previously shown to accumulate in both chronologically and photoaged human skin. We demonstrate that during dermal skin fibroblast replication in vitro in five separate cultures obtained from elderly individuals, the T414G mutant load can either increase or decrease during progressive cell division, implying the absence of consistent selection against the mutation in this context. In support of this, by utilizing a cell-sorting approach, we demonstrate that the level of the T414G mutation does not directly correlate with increased or decreased mtDNA copy number, or markers of cellular ageing including lipofuscin accumulation or ROS production. By consequence, the mutation can be distributed with a bias towards either the proliferating or senescent cell populations depending on the cell line. In conclusion, we propose that this particular mutation may have little effect on ROS production and the onset of cellular senescence in cultured fibroblasts.
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Mitochondrial dysfunction is thought to play a role in the increased levels of senescent cells observed with age.
“Mitochondrial dysfunction is thought to play a role in the increased levels of senescent cells observed with age [Passos et al., 2007; Birket et al., 2009; Passos et al., 2010] .”
From Oxidative stress and ageing (2016) · cites this paper as Birket et al., 2009
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- Authors
- Birket, M. J., Passos, J. F., von Zglinicki, T., & Birch-Machin, M. A.
- Affiliations
- Buck Institute for Research on Aging (US)
- Newcastle University (GB)
- Venue
- Journal of Investigative Dermatology
- Publisher
- Elsevier BV
- Published
- 2009-06
- Volume
- 129
- Issue
- 6
- Pages
- 1361-1366
- ISSN
- 0022-202X (ISSN-L)
- OpenAlex
- W1986200352
- Cited by
- 24
- References
- 29
- Citations by year
- 2023: 1 · 2022: 2 · 2021: 1 · 2019: 1 · 2018: 1 · 2016: 4 · 2015: 2 · 2014: 3 · 2013: 2 · 2012: 2
- FWCI
- 0.68
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Investigative Dermatology (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- Directorate for Biological Sciences
- Biotechnology and Biological Sciences Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- mitochondrial DNA, mitochondrial DNA control region, cellular senescence, reactive oxygen species, dermal fibroblasts, photoaging, chronological aging, mitochondrial DNA copy number, lipofuscin, mutational burden, cell division
- MeSH terms
- Aged, Aged, 80 and over, Biopsy, Cell Separation, Cells, Cultured, DNA, Mitochondrial, Fibroblasts, Flow Cytometry, Humans, Light, Mutation, Oxidation-Reduction, Cellular Senescence, Reactive Oxygen Species, Cell Proliferation
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