Age-associated accumulation of 8-hydroxydeoxyguanosine in mitochondrial DNA of human diaphragm

Biochem Biophys Res Commun. 1991 Sep 16;179(2):1023-9. doi: 10.1016/0006-291x(91)91921-x.


This is the first report that age-associated accumulation of 8-hydroxydeoxyguanosine (8-OH-dG) does occur in human mitochondrial DNA (mtDNA) in muscle of diaphragm. We extracted mtDNA from human diaphragm muscles from differing age groups, and determined the amount of 8-OH-dG by ultramicro-high performance liquid chromatography/mass-spectrometry system. With the same specimen, multiple deletions of mtDNA were detected by electrophoresis after amplification by the polymerase chain reaction method. In subjects below age 55, the level of 8-OH-dG in mtDNA was below 0.02% of the total deoxyguanosine (dG), whereas, in subjects over age 65, the level of 8-OH-dG increased with age at a rate of ca. 0.25% per 10 years, reaching 0.51% at age 85. Moreover, a concomitant increase in multiple deletions was detected with the increase in age. These results suggest that, in younger diaphragms, replication of mtDNA dilutes out 8-OH-dG being not detectable. In the elderly subjects aged over 65, the replication rate might be slowed down leading to the accumulation of 8-OH-dG in mtDNA, which would accelerate the age-associated multiple deletions of mtDNA observed among the subjects.

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Adult
  • Aged
  • Aged, 80 and over
  • Aging / physiology*
  • Chromatography, High Pressure Liquid
  • Chromosome Deletion
  • DNA Replication
  • DNA, Mitochondrial / metabolism*
  • Deoxyguanosine / analogs & derivatives*
  • Deoxyguanosine / genetics
  • Deoxyguanosine / metabolism
  • Diaphragm / metabolism*
  • Electrophoresis, Polyacrylamide Gel
  • Gas Chromatography-Mass Spectrometry
  • Humans
  • Male
  • Middle Aged
  • Polymerase Chain Reaction


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