MNS16A, a variable number of tandem repeats polymorphism in the TERT gene, has been suggested to regulate telomerase activity. As telomerase activity has been reported to be related to life-span, we hypothesized that ...MNS16A, a variable number of tandem repeats polymorphism in the TERT gene, has been suggested to regulate telomerase activity. As telomerase activity has been reported to be related to life-span, we hypothesized that this polymorphism might affect human longevity by controlling the length of the telomere. To test this hypothesis, we collected 446 unrelated pericentenarian individuals （age）90, mean 94.45±3.45 years） and 332 normal controls （age 22-53, mean 35.0±12.0 years） from Dujiangyan, Sichuan, China. We typed the MNS16A polymorphism in both groups, and compared the allele and genotype frequencies between the peri-centenarian and control groups using the chi-squared test. There was no significant difference between the peri-centenarian and control groups. Thus, the MNS16A polymorphism in TERT might not influence human life-span, at least in the Hart Chinese population studied here.展开更多
Calorie restriction(CR) promotes longevity among distinct organisms from yeast to mammals. Although CR-prolonged lifespan is believed to associate with enhanced respiratory activity, it is apparently controversial for...Calorie restriction(CR) promotes longevity among distinct organisms from yeast to mammals. Although CR-prolonged lifespan is believed to associate with enhanced respiratory activity, it is apparently controversial for accelerated energy consumption regardless of insufficient nutrient intake. In reconciling the contradiction of less food supply versus much metabolite dispense, we revealed a CR-based mode of dual-phase responses that encompass a phase of mitochondrial enhancement(ME) and a phase of post-mitochondrial enhancement(PME), which can be distinguished by the expression patterns and activity dynamics of mitochondrial signatures. ME is characterized by global antioxidative activation, and PME is denoted by systemic metabolic modulation. CR-mediated aging-delaying effects are replicated by artesunate, a semi-synthetic derivative of the antimalarial artemisinin that can alkylate heme-containing proteins, suggesting artesunate-heme conjugation functionally resembles nitric oxide-heme interaction. A correlation of artesunate-heme conjugation with cytochrome c oxidase activation has been established from adduct formation and activity alteration. Exogenous hydrogen peroxide also mimics CR to trigger antioxidant responses, affect signaling cascades, and alter respiratory rhythms, implying hydrogen peroxide is engaged in lifespan extension. Conclusively, artesunate mimics CR-triggered nitric oxide and hydrogen peroxide to induce antioxidative networks for scavenging reactive oxygen species and mitigating oxidative stress, thereby directing metabolic conversion from anabolism to catabolism, maintaining essential metabolic functionality, and extending life expectancy in yeast.展开更多
基金supported by the National Basic Research Program of China(2013CB530802)Yunnan Province(2011FA024)+1 种基金the National Natural Science Foundation of China(31100909)the Chinese Academy of Sciences
文摘MNS16A, a variable number of tandem repeats polymorphism in the TERT gene, has been suggested to regulate telomerase activity. As telomerase activity has been reported to be related to life-span, we hypothesized that this polymorphism might affect human longevity by controlling the length of the telomere. To test this hypothesis, we collected 446 unrelated pericentenarian individuals （age）90, mean 94.45±3.45 years） and 332 normal controls （age 22-53, mean 35.0±12.0 years） from Dujiangyan, Sichuan, China. We typed the MNS16A polymorphism in both groups, and compared the allele and genotype frequencies between the peri-centenarian and control groups using the chi-squared test. There was no significant difference between the peri-centenarian and control groups. Thus, the MNS16A polymorphism in TERT might not influence human life-span, at least in the Hart Chinese population studied here.
基金supported by grants to Zeng Qing Ping from National Natural Science Foundation of China(81273620)
文摘Calorie restriction(CR) promotes longevity among distinct organisms from yeast to mammals. Although CR-prolonged lifespan is believed to associate with enhanced respiratory activity, it is apparently controversial for accelerated energy consumption regardless of insufficient nutrient intake. In reconciling the contradiction of less food supply versus much metabolite dispense, we revealed a CR-based mode of dual-phase responses that encompass a phase of mitochondrial enhancement(ME) and a phase of post-mitochondrial enhancement(PME), which can be distinguished by the expression patterns and activity dynamics of mitochondrial signatures. ME is characterized by global antioxidative activation, and PME is denoted by systemic metabolic modulation. CR-mediated aging-delaying effects are replicated by artesunate, a semi-synthetic derivative of the antimalarial artemisinin that can alkylate heme-containing proteins, suggesting artesunate-heme conjugation functionally resembles nitric oxide-heme interaction. A correlation of artesunate-heme conjugation with cytochrome c oxidase activation has been established from adduct formation and activity alteration. Exogenous hydrogen peroxide also mimics CR to trigger antioxidant responses, affect signaling cascades, and alter respiratory rhythms, implying hydrogen peroxide is engaged in lifespan extension. Conclusively, artesunate mimics CR-triggered nitric oxide and hydrogen peroxide to induce antioxidative networks for scavenging reactive oxygen species and mitigating oxidative stress, thereby directing metabolic conversion from anabolism to catabolism, maintaining essential metabolic functionality, and extending life expectancy in yeast.
