Mitochondria have long been suspected to be among the leading determinants of aging due to their functional importance and accelerated deterioration caused by accumulation of mutations in the mitochondrial DNA. Direct repeats are known to contribute to deletion formation in mtDNA and are a powerful source of reactive oxygen species (ROS)-independent mutagenesis. To evaluate the potential importance of homology-based deletion formation, we have analyzed the association between direct repeats in the mtDNA sequence and the lifespans of 65 mammalian species. Here, we report a significant negative correlation between the mutagenic potential of direct repeats and the mammalian lifespan, which is especially evident in closely related species.