Evidence that specific mtDNA point mutations may not accumulate in skeletal muscle during normal human aging

Am J Hum Genet. 1996 Sep;59(3):591-602.


It is unclear at present whether specific mtDNA point mutations accumulate during normal human aging. In order to address this question, we used quantitative PCR of total DNA isolated from skeletal muscle from normal individuals of various ages to search for the presence and amount of spontaneous mtDNA point mutations in two small regions of the human mitochondrial genome. We observed low levels of somatic mutations above background in both regions, but there was no correlation between the amount of mutation detected and the age of the subject. These results contrasted with our finding of an age-related increase in the amount of the mtDNA "common deletion" in these very samples. Thus, it appears that both somatic mtDNA point mutations and mtDNA deletions can arise at low frequency in normal individuals but that, unlike deletions, there is no preferential amplification or accumulation of specific point mutations in skeletal muscle over the course of the normal human life span.

Publication types

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

MeSH terms

  • Adenosine Triphosphatases / genetics
  • Adolescent
  • Adult
  • Aged
  • Aging / genetics*
  • Base Sequence
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • DNA, Mitochondrial / analysis
  • DNA, Mitochondrial / genetics*
  • Hereditary Sensory and Motor Neuropathy / genetics
  • Humans
  • Infant
  • MELAS Syndrome / genetics
  • Middle Aged
  • Molecular Sequence Data
  • Muscle, Skeletal / chemistry*
  • Muscle, Skeletal / physiology
  • Point Mutation / genetics*
  • Polymerase Chain Reaction / methods
  • Sequence Deletion / genetics


  • DNA, Mitochondrial
  • Adenosine Triphosphatases