Oxidative damage to mitochondrial DNA shows marked age‐dependent increases in human brain
- 8 October 1993
- journal article
- research article
- Published by Wiley in Annals of Neurology
- Vol. 34 (4), 609-616
- https://doi.org/10.1002/ana.410340416
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/μg 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.Keywords
This publication has 45 references indexed in Scilit:
- Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosisNature, 1993
- Age-associated oxygen damage and mutations in mitochondrial DNA in human heartsBiochemical and Biophysical Research Communications, 1992
- Differential expression of cytochrome oxidase (COX) genes in different regions of monkey brainJournal of Neuroscience Research, 1992
- Multiple mitochondrial DNA deletions in an elderly human individualFEBS Letters, 1992
- Age-associated accumulation of 8-hydroxydeoxyguanosine in mitochondrial DNA of human diaphragmBiochemical and Biophysical Research Communications, 1991
- An integrated theory of aging as the result of mitochondrial-DNA mutation in differentiated cellsArchives of Gerontology and Geriatrics, 1991
- Massive conversion of guanosine to 8-hydroxy-guanosine in mouse liver mitochondrial DNA by administration of azidothymidineBiochemical and Biophysical Research Communications, 1991
- Insertion of specific bases during DNA synthesis past the oxidation-damaged base 8-oxodGNature, 1991
- Age-dependent changes in rat brain mitochondria of synaptic and non-synaptic originsMechanisms of Ageing and Development, 1987
- Regional cerebral blood flow and oxygen consumption in human aging.Stroke, 1984