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The Complicated Nature of Somatic mtDNA Mutations in Aging

Sanchez-Contreras, Monica, Kennedy, Scott R.·2022·Frontiers in Aging
DOI 10.3389/fragi.2021.805126PMC PMC8896747
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Abstract

Mitochondria are the main source of energy used to maintain cellular homeostasis. This aspect of mitochondrial biology underlies their putative role in age-associated tissue dysfunction. Proper functioning of the electron transport chain (ETC), which is partially encoded by the extra-nuclear mitochondrial genome (mtDNA), is key to maintaining this energy production. The acquisition of de novo somatic mutations that interrupt the function of the ETC have long been associated with aging and common diseases of the elderly. Yet, despite over 30 years of study, the exact role(s) mtDNA mutations play in driving aging and its associated pathologies remains under considerable debate. Furthermore, even fundamental aspects of age-related mtDNA mutagenesis, such as when mutations arise during aging, where and how often they occur across tissues, and the specific mechanisms that give rise to them, remain poorly understood. In this review, we address the current understanding of the somatic mtDNA mutations, with an emphasis of when, where, and how these mutations arise during aging. Additionally, we highlight current limitations in our knowledge and critically evaluate the controversies stemming from these limitations. Lastly, we highlight new and emerging technologies that offer potential ways forward in increasing our understanding of somatic mtDNA mutagenesis in the aging process.

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Metadata

Authors
Sanchez-Contreras, M., & Kennedy, S. R.
Venue
Frontiers in Aging
Publisher
Frontiers Media SA
Published
2022-01-10
Volume
2
ISSN
2673-6217
DOI
10.3389/fragi.2021.805126
PMC
PMC8896747
Cited by
60
References
28
Licence
creativecommons.org/licenses/by/4.0/ (vor)
Funders
  • National Institute of Diabetes and Digestive and Kidney Diseases
  • National Human Genome Research Institute
  • National Cancer Institute
  • Congressionally Directed Medical Research Programs

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