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

There has been a continuous evolution in our concept [1] that mtDNA undergo es a range of mutations with age and that such alterations lead to a declin e in mitochondrial bioenergy capacity. Here we report that a wide range of deletion mutations accumulate with age and the amount of full-length mtDNA (FLmtDNA) amplifiable by extra-long PCR (XL-PCR) markedly decreases with ag e. An analysis of single human quadriceps muscle fibres reveals a close cor relation between the decrease in FLmtDNA and the decline in cytochrome c ox idase activity, an exemplifier of mitochondrial bioenergy. However, Souther n blotting analysis of unamplified genomic DNA shows that there is little d ecrease in FLmtDNA in aged quadriceps. The results are interpreted to indic ate that while there is little change in the total mtDNA with age, nonethel ess a significant proportion of this mtDNA is extensively damaged such that it cannot be amplified by XL-PCR. The amplifiable FLmtDNA, which putativel y represents the functional component of the mtDNA, decreases markedly with age.