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

• Published in: Annals of neurology Vol. 34; no. 4; p. 609
• Main Authors: Mecocci, P, MacGarvey, U, Kaufman, A E, Koontz, D, Shoffner, J M, Wallace, D C, Beal, M F
• Format: Journal Article
• Language: English
• Published: United States 01.10.1993
• Subjects: Adult; Aged; Aged, 80 and over; Aging - metabolism; Brain - metabolism; Cell Nucleus - metabolism; Deoxyguanosine - analogs & derivatives; Deoxyguanosine - metabolism; DNA - metabolism; DNA, Mitochondrial - metabolism; Female; Humans; Male; Middle Aged; Oxidation-Reduction
• ISSN: 0364-5134; 1531-8249
• DOI: 10.1002/ana.410340416

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.