Abstract
Aging is associated with accumulation of somatic mutations. This process is especially pronounced in mitochondrial genomes of postmitotic cells, which accumulate large-scale somatic mitochondrial deletions with time, leading to neurodegeneration, muscular dystrophy and aging. Slowing down the rate of origin of these somatic deletions may benefit human lifespan and healthy aging. The main factors determining breakpoints of somatic mitochondrial deletions are direct nucleotide repeats, which might be considered as Deleterious In Late Life (DILL) alleles. Correspondingly, the decreased amount of these DILL alleles might lead to low production of somatic deletions and increased lifespan. Intriguingly, in the Japanese D4a haplogroup, which is famous for an excess of centenarians and supercentenarians, we found that the longest direct repeat (“common repeat”) in the human mitochondrial genome has been disrupted by a point synonymous mutation. Thus we hypothesize that the disruption of the common repeat annuls common deletion (which is the most frequent among all somatic deletions) and at least partially may contribute to the extreme longevity of the D4a Japanese haplogroup. Here, to better understand the mitochondrial components of longevity and potential causative links between repeats, deletions and longevity we discuss molecular, population and evolutionary factors affecting dynamics of mitochondrial direct repeats.
