Mitocondrial Haplogroup for Successful Ageing

Abstract

Japan has the world's highest longevity rate, and currently has approximately 27,000 centenarians who are 100 years old or older. Women account for around 85 percent of this group. Explanations for Japanese longevity may include their dietary habits, physical activity, and positive attitude toward life. In addition, longevity is also with genetic factors, including the mitochondrial genome (Tanaka et al, Lancet, 1998). PURPOSE: To examine the association between mitochondrial DNA and successful ageing. METHODS: We report new results from the re-analysis of 672 complete mitochondrial (mtDNA) genomes of unrelated Japanese individuals stratified into seven equal sized phenotypic groups: diabetic patients, diabetic patients with severe angiopathy, healthy non-obese young males, obese young males, patients with Alzheimer's disease, patients with Parkinson's disease and centenarians. Each phenotype had 96 samples over 27 known haplogroups: A, B4a, B4b, B4c, B*, B5, D*, F1, F2, M*, M7a, M7b, M8, M9, D4a, D4b1, D4b2, D4d, D4e, D4g, D4h, D5, G, Z, M*, N9a, and N9b. RESULTS: A t-test comparing the fraction of samples in a haplogroup to healthy young males showed a significant enrichment of haplogroups D4a, D5, and D4b2 in centenarians. The D4b2 enrichment was limited to a subgroup of 40 of 61 samples which had the synonymous mutation 9296C>T. We identified this cluster as a distinct haplogroup and labeled it as D4b2b. Using an exhaustive procedure, we constructed the complete list of "mutation patterns" for centenarians and showed that the most significant patterns were in D4a, D5, and D4b2b. CONCLUSIONS: We argue that if a selection for longevity appeared only once, it was probably an autosomal event which could be dated to after the appearance of the D mega-group but before the coalescent time of D4a, D5, and D4b2b. Using a simple procedure, we estimate that this event occurred 24.4 +/− 0.9 kYBP.