This proposal aims to investigate the origin and mechanism of accumulation of mitochondrial DNA damage in human tissues during aging. In one case a specific mitochondrial DNA deletion previously found only in patients affected with certain rare neuromuscular diseases but recently discovered in hearts and brains of normal aged individuals will be studied. The goal of this research is to determine the rate these deletions accumulate and why they accumulate to different levels in different brain regions in aged individuals. These studies may provide information on the origin of mitochondrial mutations and their contributions to aging.