Age-related mitochondrial DNA point mutations in patients with mitochondrial myopathy

J Neurol Sci. 2007 Dec 15;263(1-2):139-44. doi: 10.1016/j.jns.2007.07.006. Epub 2007 Aug 14.


Mutations in the control region (D-loop) of mitochondrial DNA (mtDNA) have been described in normal old individuals and it is suggested that they originated from oxidative damage. Respiratory chain defects may lead to increased free radical generation, increased susceptibility to oxidative damage and further increased accumulation of age-related mutations. The objective of this study was to verify whether patients with a mitochondrial disease are more predisposed to accumulate the A189G and T408A mutations in the D-loop and confirm their age-associated nature. We evaluated the presence and levels of heteroplasmy of these two mutations in muscle DNA of 52 individuals with different ages (21 age-matched controls and 31 patients with single or multiple mtDNA deletions). The frequency of both mutations was significantly increased with age, but no differences were observed comparing the group of patients with their age-matched controls. We could not observe correlation of levels of heteroplasmy with age. Our results confirm the age-related nature of the A189G and T408A mutations in the D-loop in controls and patients with mitochondrial disease, but do not suggest that patients are more predisposed to the development of age-related point mutations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aging / physiology*
  • Case-Control Studies
  • Child
  • DNA Mutational Analysis / methods
  • DNA, Mitochondrial / genetics*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mitochondrial Myopathies / genetics*
  • Mitochondrial Myopathies / physiopathology
  • Point Mutation / genetics*
  • Statistics, Nonparametric


  • DNA, Mitochondrial