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Oxidative damage to mitochondrial DNA shows marked age-dependent increases in human brain
Abstract
A major theory of aging is that oxidative damage may accumulate in DNA and contribute to physiological changes associated with aging. We examined age-related accumulation of oxidative damage to both nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) in human brain tissue. We measured the oxidized nucleoside, 8-hydroxy-2'-deoxyguanosine (OH8dG), in DNA isolated from 3 regions of cerebral cortex and cerebellum from 10 normal humans aged 42 to 97 years. The amount of OH8dG, expressed as a ratio of the amount of deoxyguanosine (dG) or as fmol/micrograms of DNA, increased progressively with normal aging in both nDNA and mtDNA; however, the rate of increase with age was much greater in mtDNA. There was a significant 10-fold increase in the amount of OH8dG in mtDNA as compared with nDNA in the entire group of samples, and a 15-fold significant increase in patients older than 70 years. These results show for the first time that there is a progressive age-related accumulation in oxidative damage to DNA in human brain, and that the mtDNA is preferentially affected. It is possible that such damage may contribute to age-dependent increases in incidence of neurodegenerative diseases.
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“Oxidation of DNA and RNA produced by ROS also occurs in AD [50,51,52,53].”
From Role of Oxidative Damage in Alzheimer’s Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery (2021) · cites this paper as [50]
In the citing paper
“It is demonstrated that there is a progressive age-related accumulation of oxidative damage to DNA in the human brain and that mtDNA is preferentially affected. The increased amount of 8-OHdG in mtDNA and nuclear DNA is demonstrated in the aging human brain and in AD [50,51,64].”
From Role of Oxidative Damage in Alzheimer’s Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery (2021) · cites this paper as [50]
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“These mtDNA mutations can be attributed to oxidative damage, at least in the brain, since the human brain mtDNA shows a marked age-related increase in oxidative damage (135).”
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Metadata
- Authors
- Mecocci, P., MacGarvey, U., Kaufman, A. E., Koontz, D., Shoffner, J. M., Wallace, D. C., & Beal, M. F.
- Affiliations
- Harvard University (US)
- Emory University (US)
- Corresponding author
- Beal, M. Flint
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 1993-10
- Volume
- 34
- Issue
- 4
- Pages
- 609-616
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- OpenAlex
- W2130753450
- Cited by
- 757
- References
- 50
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 12 · 2023: 12 · 2022: 15 · 2021: 18 · 2020: 19 · 2019: 22 · 2018: 17 · 2017: 16 · 2016: 19 · 2015: 18 · 2014: 24 · 2013: 29 · 2012: 22
- FWCI
- 7.34
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Public Health Service (16367)
- National Institute on Aging (IP50 AG05134)
- National Institute of Neurological Disorders and Stroke (NS-21328, R01NS021328)
- 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 › Molecular Biology › DNA Repair Mechanisms
- Keywords
- oxidative DNA damage, mitochondrial DNA, 8-hydroxy-2'-deoxyguanosine, brain aging, cerebral cortex, cerebellum, nuclear DNA, age-related accumulation, neurodegenerative diseases
- MeSH terms
- 8-Hydroxy-2'-Deoxyguanosine, Adult, Aged, Aged, 80 and over, Aging, Brain, Cell Nucleus, Deoxyguanosine, DNA, DNA, Mitochondrial, Female, Humans, Male, Middle Aged, Oxidation-Reduction
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