Species-specific lifespans: Can it be a lottery based on the mode of mitochondrial DNA replication?

• Accumulation of large deletions in mitochondrial DNA is one of the leading factors responsible for age-specific deterioration of mitochondria, senescence and cell loss.
• Formation of large deletions is facilitated by the unique mode of mtDNA replication that allows interactions between widely spaced direct repeats.
• Mitochondrial DNAs of long-lived species appear to have diminished potential to form deletions due to either fewer direct repeats or a switch to a less permissive mode of replication.
• I propose a testable hypothesis that explains significant differences in lifespan between species which are otherwise very similar with regard to other suspected “key” determinants of aging rate.

Accumulating evidence suggests that the aging process is, in part, driven by accumulation of large deletions in mitochondrial DNA (mtDNA). Here, I present a hypothesis that significant variations in lifespans can be explained by species-specific mtDNA sequence features that cause a shift in the mode of mtDNA replication and thus preclude the formation of large deletions.