AGING-ASSOCIATED TANDEM DUPLICATIONS IN THE D-LOOP OF MITOCHONDRIAL-DNA OF HUMAN MUSCLE

Using PCR techniques, we detected a similar to 260 bp (type I) and a s imilar to 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 duplicati on. About 90% of the subjects harbouring the duplicated mtDNAs also ha d the 4,977 bp deletion. Moreover, the incidence and quantity of the t ype 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 wa s 3.1% while that of a 55-year-old individual was only 0.78%. We sugge st that the tandem duplications occur alone or with mtDNA deletions in human tissues in an age-dependent manner, and thereby cause synergist ic deleterious effects on mitochondrial respiratory functions in human ageing.