AGE-ASSOCIATED MITOCHONDRIAL-DNA DELETIONS IN MOUSE SKELETAL-MUSCLE -COMPARISON OF DIFFERENT REGIONS OF THE MITOCHONDRIAL GENOME

The abundance of mitochondrial DNA (mtDNA) deletions has been shown to increase with age in a number of species and may contribute to the ag ing process. Estimating the total mtDNA deletion load of an individual is essential in evaluating the potential physiological impact. in thi s study, we compared three 5-kb regions of the mitochondrial genome: o ne in the major are, one in the minor are, and a third containing the light strand origin of replication. Through PCR analysis of mouse skel etal muscle, we have determined that not all regions produce equal num bers of age-associated deletions. There are, on average, twofold more detectable deletions in the major are region than in the minor are reg ion. Deletions that result in the loss of the light strand origin of r eplication are rarely detected. Furthermore, the mechanism of deletion formation seems to be similar in both the major and minor arcs, with direct repeats playing an important, although not essential, role. (C) 1996 Wiley-Liss, Inc.