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Mitochondrial DNA deletions in human brain: regional variability and increase with advanced age
Abstract
We have examined the role of somatic mitochondrial DNA (mtDNA) mutations in human ageing by quantitating the accumulation of the common 4977 nucleotide pair (np) deletion (mtDNA4977) in the cortex, putamen and cerebellum. A significant increase in the mtDNA4977 deletion was seen in elderly individuals. In the cortex, the deleted to total mtDNA ratio ranged from 0.00023 to 0.012 in 67-77 year old brains and up to 0.034 in subjects over 80. In the putamen, the deletion level ranged from 0.0016 to 0.010 in 67 to 77 years old up to 0.12 in individuals over the age of 80. The cerebellum remained relatively devoid of mtDNA deletions. Similar changes were observed with a different 7436 np deletion. These changes suggest that somatic mtDNA deletions might contribute to the neurological impairment often associated with ageing.
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“Evidence indicates age-related mtDNA changes do in fact occur within the human brain.”
From Brain aging, Alzheimer's disease, and mitochondria (2011) · cites this paper as [115]
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“Levels of a 5-kilobase deletion that particularly affects mtDNA COX genes increase with age [115].”
From Brain aging, Alzheimer's disease, and mitochondria (2011) · cites this paper as [115]
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Estudo dos mecanismos moleculares do reparo de quebra de duplas fitas no DNA mitocondrial
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Yan, Y., & Jiao, R. (2015) · Wiley eBooks · doi:10.1002/9781119017127.ch6 · Cited by 1
Metadata
- Authors
- Corral-Debrinski, M., Horton, T., Lott, M. T., Shoffner, J. M., Flint Beal, M., & Wallace, D. C.
- Affiliations
- Emory University (US)
- Venue
- Nature Genetics
- Published
- 1992-12
- Volume
- 2
- Issue
- 4
- Pages
- 324-329
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W1973851166
- Cited by
- 890
- References
- 43
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 19 · 2023: 12 · 2022: 25 · 2021: 19 · 2020: 23 · 2019: 36 · 2018: 21 · 2017: 28 · 2016: 21 · 2015: 32 · 2014: 23 · 2013: 32 · 2012: 24
- FWCI
- 10.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- 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 › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Keywords
- mitochondrial DNA deletions, somatic mtDNA mutations, human aging, brain aging, cerebral cortex, putamen, cerebellum, regional variation, neurological deficit
- MeSH terms
- Adult, Aged, Aged, 80 and over, Aging, Base Sequence, Brain, DNA Damage, DNA, Mitochondrial, Female, Humans, Male, Molecular Sequence Data, Oxidative Phosphorylation, Tissue Distribution, Sequence Deletion
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