Ageing-associated tandem duplications in the D-loop of mitochondrial DNA of human muscle

Using PCR techniques, we detected a ∼260 bp (type I) and a ∼200 bp (type II) tandem duplications in the mtDNA of muscle biopsies from aged individuals. Only one 70-year-old subject was found to harbour the type I and 28 out of 58 subjects had type II duplication. About 90% of the subjects harbouring the duplicated mtDNAs also had the 4,977 bp deletion. Moreover, the incidence and quantity of the type II duplication were found to increase with age. The proportion of the type II duplicated mtDNA in the muscle of a 71-year-old subject was 3.1% while that of a 55-year-old individual was only 0.78%. We suggest that the tandem duplications occur alone or with mtDNA deletions in human tissues in an age-dependent manner, and thereby cause synergistic deleterious effects on mitochondrial respiratory functions in human ageing.