Contribution of genetic polymorphisms on functional status at very old age: a gene-based analysis of 38 genes (311 SNPs) in the oxidative stress pathway.
Contribution of genetic polymorphisms on functional status at very old age: a gene-based analysis of 38 genes (311 SNPs) in the oxidative stress pathway.
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遗传多态性对非常老年功能状态的贡献：基于基因的氧化应激途径中38个基因（311 SNP）的分析。
DOI：
10.1016/j.exger.2014.01.014
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发表时间：
2014-04
影响因子：
3.9
通讯作者：
Christiansen, L.
中科院分区：
文献类型：
--
作者：
Dato, S.;Soerensen, M.;Lagani, V.;Montesanto, A.;Passarino, G.;Christensen, K.;Tan, Q.;Christiansen, L.
功能的保存是一个公认的长寿标志。在分子水平上，随着衰老发生的生理衰退的主要决定因素是对大分子的氧化损伤的产生和积累之间的不平衡，以及避免或修复这种损伤的应激反应效率降低。在本文中，我们调查了38个基因（311个SNPs）属于前抗氧化剂通路与身体和认知性能的关联，通过分析单个SNP和基因为基础的关联与握力（HG），日常生活活动（ADL），步行速度（WS），简易精神状态检查（MMSE）和综合认知评分（CCS）在一个队列的1089名丹麦90岁。此外，对于在促抗氧化剂途径中分析的每个基因，我们测试了对纵向存活的影响。在整个样本中，TXNRD 1变异性与ADL和WS，NDUF S1和UCP 3与HG和WS，GCLC和UCP 2与WS存在名义相关性（p < 0.05）。MMSE与NDUFV1、MT1A和GSTP1变异性之间存在更强的相关性（p < 0.009），尽管没有多重比较校正。此外，我们发现，在促抗氧化剂途径和功能状态在老年的遗传变异之间的关联是受性别的影响。特别是，最显着的关联，观察到在90岁的女性，HG评分和GLRX和UCP3变异，ADL水平和TXNRD1，MMSE和MT1A遗传变异之间。在男性中，发现UQCRFS1基因与ADL水平的边缘统计学显著相关。在女性样本中，仅发现SOD 2、NDUF S1、UCP 3和TXNRD 1变异性与生存率存在名义上的显著相关性，后两者证实了同一队列中报告的先前观察结果。总的来说，我们的工作支持属于促抗氧化途径的基因能够在生命的第九个十年后调节身体和认知能力，最终影响极端生存的证据。
Preservation of functional ability is a well-recognized marker of longevity. At a molecular level, a major determinant of the physiological decline occurring with aging is the imbalance between production and accumulation of oxidative damage to macromolecules, together with a decreased efficiency of stress response to avoid or repair such damage. In this paper we investigated the association of 38 genes (311 SNPs) belonging to the pro–antioxidant pathways with physical and cognitive performances, by analyzing single SNP and gene-based associations with Hand Grip strength (HG), Activities of Daily Living (ADL), Walking Speed (WS), Mini Mental State Examination (MMSE) and Composite Cognitive Score (CCS) in a Cohort of 1089 Danish nonagenarians. Moreover, for each gene analyzed in the pro–antioxidant pathway, we tested the influence on longitudinal survival. In the whole sample, nominal associations were found for TXNRD1 variability with ADL and WS, NDUFS1 and UCP3 with HG and WS, GCLC and UCP2 with WS (p < 0.05). Stronger associations although not holding the multiple comparison correction, were observed between MMSE and NDUFV1, MT1A and GSTP1 variability (p < 0.009). Moreover, we found that association between genetic variability in the pro–antioxidant pathway and functional status at old age is influenced by sex. In particular, most significant associations were observed in nonagenarian females, between HG scores and GLRX and UCP3 variability, between ADL levels and TXNRD1, MMSE and MT1A genetic variability. In males, a borderline statistically significant association with ADL level was found for UQCRFS1 gene. Nominally significant associations in relation to survival were found in the female sample only with SOD2, NDUFS1, UCP3 and TXNRD1 variability, the latter two confirming previous observations reported in the same cohort. Overall, our work supports the evidence that genes belonging to the pro–anti-oxidant pathway are able to modulate physical and cognitive performance after the ninth decade of life, finally influencing extreme survival.
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影响因子：
--
作者：
Dato, Serena;Montesanto, Alberto;Passarino, Giuseppe
通讯作者：
Passarino, Giuseppe
影响因子：
168.9
作者：
Christensen, Kaare;Doblhammer, Gabriele;Rau, Roland;Vaupel, James W.
通讯作者：
Vaupel, James W.
DOI：
10.1073/pnas.0804931105
发表时间：
2008-09-09
影响因子：
11.1
作者：
Christensen, Kaare;McGue, Matt;Vaupel, James W.
通讯作者：
Vaupel, James W.
影响因子：
6.7
作者：
Kulminski, Alexander;Ukraintseva, Svetlana V.;Yashin, Anatoli I.
通讯作者：
Yashin, Anatoli I.
影响因子：
5.3
作者：
Dato, Serena;Soerensen, Mette;Montesanto, Alberto;Lagani, Vincenzo;Passarino, Giuseppe;Christensen, Kaare;Christiansen, Lene
通讯作者：
Christiansen, Lene