Damage to mitochondrial DNA (mtDNA) has been proposed to play a major role in the aging process. An increasing number of studies have shown that mtDNA mutations are involved in diseases involving muscle weakness and encephalopathy, but also include diabetes and other syndromes. In addition, marked increases in specific human tissues have been shown with increasing age. In an effort to assess the universality of this age-dependence, we have sought evidence of deletions in mtDNA in various tissues of young and old rats. We identified a 4.8 kb deletion which showed striking increases with age, perhaps suggesting common causes. The tissue distribution of the changes mimic those seen in human mitochondria with age. An altered form of mtDNA that appears to be an intermediate in the deletion process was also found and corresponds to one observed in human diseases. MtDNA damage leading to these changes may be important in muscle weakness, neurodegeneration and other age associated disabilities.
