Cited by 757Mitochondrial Function and PathologyGenetics, Aging, and Longevity in Model OrganismsDNA Repair Mechanisms

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Oxidative damage to mitochondrial DNA shows marked age-dependent increases in human brain

Mecocci, Patrizia, MacGarvey, Usha, Kaufman, Allan E., Koontz, Deborah, Shoffner, John M., Wallace, Douglas C., Beal, M. Flint·1993·Annals of Neurology

DOI 10.1002/ana.410340416

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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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MethodResult
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“Mecocci et al. (1993) were the ﬁrst group to demonstrate a progressive age-related accumulation of 8-OHdG in the cerebral cortex of cognitively normal subjects, aged 42–97 years.”

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
ORCID: Mecocci, Patrizia
Shoffner, John M.
Wallace, Douglas C.
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
DOI: 10.1002/ana.410340416
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
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 4025 d)
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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Oxidative damage to mitochondrial DNA shows marked age-dependent increases in human brain

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