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

Ann Neurol. 1993 Oct;34(4):609-16. 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Adult
  • Aged
  • Aged, 80 and over
  • Aging / metabolism*
  • Brain / metabolism*
  • Cell Nucleus / metabolism
  • DNA / metabolism
  • DNA, Mitochondrial / metabolism*
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / metabolism
  • Female
  • Humans
  • Male
  • Middle Aged
  • Oxidation-Reduction*


  • DNA, Mitochondrial
  • 8-Hydroxy-2'-Deoxyguanosine
  • DNA
  • Deoxyguanosine