Oxidative damage to DNA accumulates with age in the brain, particularly in mitochondrial DNA (mtDNA). Oxidatively DNA damage can induce point mutations. mtDNA point mutations accumulate with age in the brain, with mutation levels correlating inversely with mitochondrial function. Somatic mtDNA point mutations also accumulate within certain cancers. We are studying the accumulation of mtDNA point mutations in single neurons in the brain and the potential role of these mutations in aging and age-related neurodegeneration. In addition, we are studying the role of mitophagy and the mTOR pathway in regulating levels of somatic mtDNA mutations. These data have potential relevance to aging, age-related neurodegenerative disorders, and cancer.