Age-associated oxygen damage and mutations in mitochondrial DNA in human hearts

Biochem Biophys Res Commun. 1992 Dec 15;189(2):979-85. doi: 10.1016/0006-291x(92)92300-m.


Some mutations in mitochondrial DNA (mtDNA) causing a number of neuromuscular diseases are suggested to arise spontaneously during the life of an individual. To substantiate the extent and the rate of these somatic mutations, mtDNA specimens from post-mortem human heart muscles of subjects in differing age groups were hydrolyzed. 8-Hydroxy-deoxyguanosine (8-OH-dG), a hydroxyl-radical adduct of deoxyguanosine, in mtDNA, was quantitatively determined using a micro high-performance liquid chromatography/mass spectrometry system. In each specimen, the mtDNA with a 7.4 kilo base-pair deletion was quantified by the kinetic polymerase chain reaction method. In association with age, the 8-OH-dG content accumulated exponentially up to 1.5% with a correlative increase in the content of the deleted mtDNA up to 7%. Clear correlation between the 8-OH-dG content in mtDNA and the population of mtDNA with a deletion (r = 0.93, P < 0.01) gives insight into the mechanism for the generation of a large deletion. These results indicate that accumulation of somatically acquired oxygen damage together with age-associated mutations in mtDNA which lead to bioenergetic deficiency and the heart muscle weakness are inevitable in human life.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Adult
  • Aged
  • Aged, 80 and over
  • Aging / genetics*
  • Base Sequence
  • Chromatography, High Pressure Liquid
  • DNA Damage*
  • DNA, Mitochondrial / genetics*
  • DNA, Mitochondrial / isolation & purification
  • Deoxyguanosine / analogs & derivatives*
  • Deoxyguanosine / analysis
  • Female
  • Heart / physiology*
  • Humans
  • Male
  • Mass Spectrometry
  • Middle Aged
  • Mitochondria, Heart / physiology
  • Models, Genetic
  • Molecular Sequence Data
  • Oxygen / toxicity*
  • Point Mutation*
  • Sequence Deletion*


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