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Background  In centenarian populations, application of the positive biology approach (examination of positive phenotypes in aging) has revealed that mitochondrial DNA (mtDNA) mutation accumulation may be linked to human longevity; however, the role of guanine nucleotide-binding protein (G protein) abnormalities modulated by G-protein beta-3 ( GNB3 ) and nitrate (NO2) production associated with endothelial nitric oxide synthase ( eNOS ), commonly appearing in age-related diseases, remains undetermined.    Objective  The association between the mtDNA 5178A/C, mtDNA 10398A/G,  GNB3 C825T , and  eNOS  polymorphisms and longevity in a Uygur population (Xinjiang region, China) were investigated.    Methods  A total of 275 experimental subjects aged ≥100 or with 4 generations currently living were screened for inclusion in the centenarian (>100 years) and nonagenarian groups (90–100 years), and 112 65–70 year old control subjects were selected. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to examine mtDNA 5178A/C, mtDNA 10398A/G,  GNB3 C825T , and  eNOS . Associations between polymorphic loci, genotypes, and longevity were analyzed.    Results  165 included subjects (M∶F = 107∶58; mean age = 97±3 years; mean age 100–113 years) were assigned to the centenarian (M∶F = 46/19;  n  = 65) and nonagenarian groups (M∶F = 61/39;  n  = 100). Associations between mtDNA C5178A and A10398G polymorphisms with longevity in the centenarian group with mtDNA genotype frequencies 5178A and 10398G were 66.79% and 36.8%.    Conclusions  Applying the overwhelming longevity observed in Uygur populations, these findings demonstrate that mtDNA 5178A/C and 10398A/G,  GNB3 C825T , and  eNOS  polymorphisms are useful as a genetic basis for longevity.

GNB3, eNOS, and Mitochondrial DNA Polymorphisms Correlate to Natural Longevity in a Xinjiang Uygur Population