Golden mean to longevity: rareness of mitochondrial cytochrome b variants in centenarians but not in patients with Parkinson's disease.
To test the hypothesis that centenarians are free from deleterious mitochondrial variations, we analyzed amino acid variations in the cytochrome b molecule 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 rareness of amino acid variations in contrast to the variety of amino acid replacements in patients with Parkinson's disease. These results suggest that centenarians are genetically hitting the "golden mean" (less variation from the consensus cytochrome b sequence or less mismatch with other subunits). A multiplex detection system for various deleterious variations in combination with genetic tests for longevity-associated genotypes will be necessary to predict longevity or age-related diseases.
Tanaka
Masashi
M
Department of Gene Therapy, Gifu International Institute of Biotechnology, Mitake, Gifu, Japan. mtanaka@giib.or.jp
Fuku
Noriyuki
N
Takeyasu
Takeshi
T
Guo
Li-Jun
LJ
Hirose
Raita
R
Kurata
Miyuki
M
Borgeld
Harm-Jan W
HJ
Yamada
Yoshiji
Y
Maruyama
Wakako
W
Arai
Yasumichi
Y
Hirose
Nobuyoshi
N
Oshida
Yoshiharu
Y
Sato
Yuzo
Y
Hattori
Nobutaka
N
Mizuno
Yoshikuni
Y
Iwata
So
S
Yagi
Kunio
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over / Q000502:physiology*; D000595:Amino Acid Sequence / Q000235:genetics; D001483:Base Sequence / Q000235:genetics; D003573:Cytochrome b Group / Q000172:deficiency* / Q000235:genetics; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D003920:Diabetes Mellitus / Q000235:genetics; D005820:Genetic Testing; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008136:Longevity / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D009765:Obesity / Q000235:genetics; D010085:Oxidative Phosphorylation; D018384:Oxidative Stress / Q000235:genetics; D010300:Parkinson Disease / Q000235:genetics*; D017354:Point Mutation / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D017434:Protein Structure, Tertiary / Q000235:genetics
D003573:Cytochrome b Group; D004272:DNA, Mitochondrial