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The age-associated decrease in the amount of amplifiable full-length mitochondrial DNA in human skeletal muscle

S A Kovalenko1, G Kopsidas, M M Islam

  • 1Centre For Molecular Biology and Medicine, Epworth Medical Centre, Melbourne, Victoria, Australia. SKovalenko@cmbm.com.au

Biochemistry and Molecular Biology International
|January 19, 1999
PubMed
Summary
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Mitochondrial DNA (mtDNA) mutations increase with age, reducing energy production. Functional, amplifiable mtDNA declines significantly in aging muscle, despite total mtDNA levels remaining stable.

Area of Science:

  • Cellular and Molecular Biology
  • Aging Research
  • Mitochondrial Biology

Background:

  • Mitochondrial DNA (mtDNA) mutations are linked to aging and decreased cellular energy production.
  • The precise impact of age-related mtDNA alterations on functional capacity requires further elucidation.

Purpose of the Study:

  • To investigate the age-related changes in full-length mtDNA (FLmtDNA) and its correlation with mitochondrial bioenergy.
  • To determine if total mtDNA content or the integrity of mtDNA changes with age in human muscle.

Main Methods:

  • Analysis of single human quadriceps muscle fibers.
  • Extra-long PCR (XL-PCR) to quantify amplifiable FLmtDNA.
  • Measurement of cytochrome c oxidase activity as a marker of mitochondrial bioenergy.

Related Experiment Videos

  • Southern blotting of unamplified genomic DNA to assess total FLmtDNA.
  • Main Results:

    • A wide range of mtDNA deletion mutations accumulate with age.
    • The amount of amplifiable FLmtDNA significantly decreases with age in human quadriceps muscle.
    • A strong correlation exists between reduced amplifiable FLmtDNA and diminished cytochrome c oxidase activity.
    • Southern blotting indicates minimal change in total FLmtDNA content in aged muscle.

    Conclusions:

    • Age-related mtDNA damage, rather than a decrease in total mtDNA quantity, leads to reduced functional mtDNA.
    • The decline in amplifiable FLmtDNA with age correlates with impaired mitochondrial bioenergetics.
    • This suggests that accumulated mtDNA damage is a key factor in age-associated decline of mitochondrial function.