Mitochondrial mutations accumulate with aging; such mutations impair mitochondrial function and result in increased production of reactive oxygen species (ROS), which in turn damage DNA and lead to more mutations. How do these mutations arise in the first place? Krishnan et al. meta-analyze the literature on the subject and conclude:
mtDNA deletions are most likely to occur during repair of damaged mtDNA rather than during replication. This conclusion has important implications for prevention of mtDNA disease and, potentially, for our understanding of the aging process.
Damn right: If repair were the main source of mitochondrial deletion mutations, it would be a lot harder to imagine useful interventions. If, however, damage (from both intrinsic and extrinsic sources) is the main culprit, we might hope to prevent the mutations by preventing the damage in the first place (e.g., using mitochondrially targeted ROS scavengers).