Nucleotide repeats in mitochondrial genome determine human lifespan
Direct nucleotide repeats can facilitate deletions of segments of mitochondrial genome1, leading to a wide range of neuromuscular disorders1,2 as well as aging2,3 in humans. We hypothesized that the number of the direct perfect repeats in human mitochondrial genomes influences longevity through the formation of harmful mtDNA deletions in the somatic cells. The analysis of the complete mitochondrial genomes of 762 unrelated Japanese individuals4-6 reveals a negative correlation between the abundance of the direct perfect repeats and the expected longevity. This association is largely due to the disruption of the common repeat (8470,13447) by a point mutation 8473C which occurred at the origin of the D4a haplogroup characterized by extreme longevity in Japan7. Our results provide the first evidence for correlation between the number of nucleotide repeats and the lifespan on intraspecific level.