High mutational burden in the mtDNA control region from aged muscles: A single-fiber study

Roberto Del Bo, Marco Crimi, Monica Sciacco, Giulia Malferrari, Andreina Bordoni, Laura Napoli, Alessandro Prelle, Ida Biunno, Maurizio Moggio, Nereo Bresolin, Guglielmo Scarlato, Giacomo Pietro Comi

Research output: Contribution to journalArticlepeer-review


The ageing process is associated with the accumulation of somatic mutations of mitochondrial DNA (mtDNA). The aged human skeletal muscle tissue presents a mosaic of fibers when stained histochemically for cytochrome c oxidase (COX) activity with a proportion of COX negative fibers. Given the potential relevance of any alteration in the mtDNA control region for replication, we analysed the correlation between the presence of mutations and their degree of heteroplasmy and the COX phenotype in individual muscle fibers of aged healthy donors. A region of the mtDNA D-loop was cloned from single fiber-derived DNA and multiple clones were analysed. This strategy showed that a high level of mutational burden is present in all fibers and that several types of mtDNA rearrangements are detectable: recurrent (A189G, T408A and T414G) and rare point mutations, length variations affecting the homopolymeric tract and the (CA)n repeat and macrodeletions. The aggregate mutational load in the D-loop region correlated with the single fiber COX phenotype, suggesting that the cumulative burden of multiple, individually rare, mtDNA alterations might functionally impair the mitochondrial genetic machinery.

Original languageEnglish
Pages (from-to)829-838
Number of pages10
JournalNeurobiology of Aging
Issue number6
Publication statusPublished - Oct 2003


  • Ageing
  • Mitochondrial DNA
  • Muscle
  • Single fiber
  • Somatic point mutations

ASJC Scopus subject areas

  • Clinical Neurology
  • Biological Psychiatry
  • Developmental Neuroscience
  • Neurology
  • Psychology(all)


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