The role of genetics in longevity and aging processes is complex and controversial. In invertebrate and mammal life-span studies, researchers found that having or lacking certain variations can extend animals life-span significantly, which became “longevity” candidate genes. Most of the candidate genes are evolutionary conserved and involved in regulating metabolic pathways, promoting or attenuating longevity and age-onset disease susceptibility in humans. Centenarians and their offsprings have lower all-cause mortality than normal population and the longevity pedigree and siblings studies show that longevity has 25~30% hereditary capacity. People have higher age related and fatal diseases mortality at advanced age and the influence of genetic factors that influence survival and health become more evident with age advancing. On the one hand, several studies show that longevity populations may lack genetic risk factors, which make them delay or avoid the fatal diseases. On the other hand, studies show that longevity populations may have more longevity assurance genes, which make them healthier by attenuating the risk of fatal diseases. Genetic risk factors and longevity genes are important in influencing longevity, however, the mode of their contribution to longevity is still unknown. Studying the mechanism of human longevity enables us to better understand longevity, aging and pathology of age-onset diseases.To disentangle the roles of genetic risk factors and longevity assurance genes in human longevity, we tested 24 disease predisposing SNPs and 24 longevity association SNPs in Sichuan populations from China. After association study, we found 7 disease risk SNPs have significant lower frequency in Sichuan population than the normal population. There SNPs are most related to cardiovascular disease and stoke. In addition, 5 longevity association SNPs are found have significant higher frequency in longevity population than the normal population. The results suggest that longevity population not only lacks the genetic risk factors, but also has longevity assurance genes.In addition to the nuclear genomes, influences of the mitochondrial genome in longevity and aging cannot be neglected. In 1950s, the free radical theory of aging was proposed and is still on a hot debate. Numerous mitochondrial DNA lineages have been reported to associate with longevity in different populations, nonetheless, it is still a controversy of the association of longevity and mitochondrial DNA haplogroup. Besides, the quantitative character of mitochondrial DNA has been reported to be associated with aging and age related diseases. Centenarians are escaper and survivor of fatal diseases, so we hypothesis that centenarians have a unique mechanism of oxidative stress resistance. To test our hypothesis, we test the mitochondrial DNA haplogroup association with longevity and the quantitative character of longevity population and younger populations in Hainan populations. The results show that there is no correlation between longevity and mitochondrial DNA haplogroup. However, we find that centenarians maintains a relatively higher level of mitochondrial DNA content compare to the aged populations. To verify this finding, we examine the mitochondrial DNA content in Sichuan populations. The results show a same pattern that we found in Hainan population. We conclude that longevity is associated with mitochondrial DNA content, but not the haplogroup.
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