Mitochondrial-derived peptides (MDP) are encoded by functional short open reading frames in the mitochondrial DNA (mtDNA). These include humanin, and the recently discovered mitochondrial open reading frame of the 12S rRNA-c (MOTS-c). Although more research is needed, we suggest that the m.1382A>C polymorphism located in the MOTS-c encoding mtDNA, which is specific for the Northeast Asian population, may be among the putative biological mechanisms explaining the high longevity of Japanese people.