Mitochondrial genotypes and cytochrome b variants associated with longevity or Parkinson's disease.
We are currently sequencing the entire mitochondrial genome from 600 persons, including centenarians, patients with Parkinson's disease or diabetes, and young adults with or without obesity to search for single nucleotide polymorphisms (SNPs) associated with longevity or diseases. To test the hypothesis that centenarians are free from deleterious mitochondrial variations, we analyzed amino acid variations in cytochrome b of 64 Japanese centenarians. Although the frequencies of some variations, such as N260D and G251S, differed significantly between centenarians and patients with Parkinson's disease, the most striking feature of centenarian cytochrome b was the much greater scarceness of amino acid variations in contrast with the variety of amino acid replacements in patients with Parkinson's disease. Particular deviations from the standard amino acid sequence may be associated with increased production by mitochondria of reactive oxygen species. The absence of certain variations in centenarians and their presence in patients with Parkinson's disease indicate that these variations do not benefit long-term survival but do predispose to adult-onset diseases and that centenarians are genetically hitting the "golden mean."
Tanaka
Masashi
M
Department of Gene Therapy, Gifu International Institute of Biotechnology, Yagi Memorial Park, Mitake, Gifu 505-0116, Japan. mtanaka@giib.or.jp
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics / Q000378:metabolism; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D001208:Asia / Q000453:epidemiology; D015897:Comorbidity; D003324:Coronary Artery Disease / Q000453:epidemiology / Q000235:genetics; D003573:Cytochrome b Group / Q000235:genetics*; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics; D003920:Diabetes Mellitus / Q000453:epidemiology / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008136:Longevity / Q000235:genetics*; D008322:Mammals / Q000235:genetics; D008928:Mitochondria / Q000201:enzymology* / Q000235:genetics*; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism
D003573:Cytochrome b Group; D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species