Differential occurrence of mutations in mitochondrial DNA of human skeletal muscle during aging

Hum Mutat. 1998;11(5):360-71. doi: 10.1002/(SICI)1098-1004(1998)11:5<360::AID-HUMU3>3.0.CO;2-U.


Seven mtDNA mutations (five base substitutions and two deletions) were studied in skeletal muscle samples of 18 human subjects aged 1 hr to 90 years. Quantitative PCR procedures were applied to determine the incidence (frequency of occurrence) and abundance (percentage of mutant mtDNA out of total mtDNA). The base substitutions, in general, showed a very early onset, three such mutations being detectable in the muscles of infants aged 1 hr and 5 weeks. Of two disease-associated point mutations studied, 3243 A-->G showed significant accumulation with age (P < 0.05), while 8993 T-->G showed no significant age accumulation (P > 0.1). Moreover, three arbitrarily chosen mutations (not disease-associated) showed no age-associated accumulation: two (7029 C-->T and 7920 A-->G) showed little change over the years (P > 0.1), while the other (13167 A-->G) showed a significant decrease (P < 0.05). both the 4,977-bp and 7,436-bp deletions showed a significant age-associated occurrence (P < 0.01 and P < 0.05, respectively). The age of onset of detectable deletions is about 20-40 years; thereafter, the incidence and abundance of deletions tend to increase as a function of advancing age. The seven specific mutations were found to occur independent of each other, indicating the random nature of mtDNA mutations in skeletal muscle. Moreover, the age-associated accumulation of multiple deletions was observed in the same set of muscle tissues, each extract displaying a unique set of multiple PCR products. Thus, mutations in mtDNA occur differentially in human skeletal muscle during aging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Aging / genetics*
  • Alleles
  • Base Sequence
  • Child
  • Child, Preschool
  • DNA, Mitochondrial / genetics*
  • Humans
  • Infant
  • Infant, Newborn
  • Middle Aged
  • Mitochondria, Muscle / genetics*
  • Muscle, Skeletal / chemistry*
  • Point Mutation*
  • Polymerase Chain Reaction
  • Sequence Analysis, DNA
  • Sequence Deletion*


  • DNA, Mitochondrial