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首页> 外文期刊>Mechanisms of Ageing and Development >The Mn-superoxide dismutase single nucleotide polymorphism rs4880 and the glutathione peroxidase 1 single nucleotide polymorphism rs1050450 are associated with aging and longevity in the oldest old.
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The Mn-superoxide dismutase single nucleotide polymorphism rs4880 and the glutathione peroxidase 1 single nucleotide polymorphism rs1050450 are associated with aging and longevity in the oldest old.

机译：锰超氧化物歧化酶单核苷酸多态性rs4880和谷胱甘肽过氧化物酶1单核苷酸多态性rs1050450与最老的老年人的衰老和寿命有关。

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摘要

The free radical theory of aging states that reactive oxygen species (ROS) play a key role in age-related accumulation of cellular damage, and consequently influence aging and longevity. Therefore, variation in genes encoding proteins protecting against ROS could be expected to influence variation in aging and life span. The rs4880 and rs1050450 SNPs in the manganese superoxide dismutase (MnSOD) and glutathione peroxidase 1 (GPX1) genes, respectively, are associated with age-related diseases and appear to affect the activities of the encoded variant proteins. In this study we genotyped these SNPs in 1650 individuals from the Danish 1905 cohort (follow-up time: 1998-2008, age at intake: 92-93 years, number of deaths: 1589 (96.3%)) and investigated the association with aging and longevity. We found decreased mortality of individuals holding either the MnSOD rs4880 C or the GPX1 rs1050450 T alleles (HR (MnSOD(CC/CT))=0.91, P=0, p=0.002 and HR (GPX1(TT/TC))=0.93, p=0.008). Furthermore, a synergetic effect of the alleles was observed (HR=0.76, p=0.001). Finally, moderate positive associations with good self rated health, decreased disability and increased cognitive capacity were observed. Our results thus indicate that genetic variation in MnSOD and GPX1 may be associated with aging and longevity.
机译：衰老的自由基理论指出，活性氧（ROS）在与年龄相关的细胞损伤累积中起关键作用，因此会影响衰老和寿命。因此，可以预期编码保护ROS的蛋白质的基因的变异会影响衰老和寿命的变异。锰超氧化物歧化酶（MnSOD）和谷胱甘肽过氧化物酶1（GPX1）基因中的rs4880和rs1050450 SNP分别与年龄相关疾病有关，并似乎影响编码的变异蛋白的活性。在这项研究中，我们对来自丹麦1905年队列的1650名个体的这些SNP进行了基因分型（随访时间：1998-2008年，入院年龄：92-93岁，死亡人数：1589（96.3％）），并调查了与衰老的关系和长寿。我们发现持有MnSOD rs4880 C或GPX1 rs1050450 T等位基因（HR（MnSOD（CC / CT））= 0.91，P = 0，p = 0.002和HR（GPX1（TT / TC））= 0.93的个体的死亡率降低，p = 0.008）。此外，观察到等位基因的协同作用（HR ＝ 0.76，p ＝ 0.001）。最后，观察到具有良好自我评价健康，残疾减少和认知能力增强的中度积极关联。因此，我们的结果表明MnSOD和GPX1的遗传变异可能与衰老和寿命有关。

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