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首页> 外文期刊>The journals of gerontology.Series A. Biological sciences and medical sciences >Zinc-Induced Metallothionein in Centenarian Offspring From a Large European Population: The MARK-AGE Project
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Zinc-Induced Metallothionein in Centenarian Offspring From a Large European Population: The MARK-AGE Project

机译：锌诱导的欧洲人口百年代人口中的金属硫蛋白：标志性项目

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Metallothionein (MT) family are cysteine-rich proteins that regulate zinc (Zn) homeostasis and protect against oxidative damage. Studies in transgenic mice have shown that MT favorably influence longevity, although their role in human aging is not completely understood. Within the European multicenter study MARK-AGE, we analyzed MT induction after Zn treatment in peripheral blood mononuclear cells (PBMCs) and its relation with redox biomarkers in 2,936 age-stratified subjects (35-75 years) including the general population (RASIG), centenarian offspring (GO), and their spouses (SGO). We found that the lymphocyte capability to induce MT in response to Zn is not affected by aging. However, GO participants showed lower Zn-induced MT and increased basal expression of MT1A, MT1X, and ZnT-1 genes than RASIG subjects. Moreover, Zn-induced MT levels were found to be inversely related with oxidative stress markers (plasma protein carbonyls, 3-nitrotyrosine, and malondialdehyde) in the whole population, but not in GO subjects. In conclusion, our results support the hypothesis that the response to Zn is attenuated in PBMCs of centenarian offspring compared to the general population as a consequence of a tighter control of Zn homeostasis which is likely to provide them constant protection against stress stimuli over the whole lifespan.
机译：金属硫蛋白（MT）家族是富含半胱氨酸的蛋白质，调节锌（Zn）稳态，防止氧化损伤。对转基因小鼠的研究表明，MT有利于延长寿命，尽管它们在人类衰老中的作用尚不完全清楚。在欧洲多中心研究MARK-AGE中，我们分析了2936名年龄分层受试者（35-75岁）外周血单个核细胞（PBMC）接受锌治疗后的MT诱导及其与氧化还原生物标记物的关系，包括普通人群（RASIG）、百岁老人后代（GO）及其配偶（SGO）。我们发现淋巴细胞对锌诱导MT的能力不受衰老的影响。然而，GO受试者与RASIG受试者相比，锌诱导的MT较低，MT1A、MT1X和ZnT-1基因的基础表达增加。此外，在整个人群中，锌诱导的MT水平与氧化应激标记物（血浆蛋白羰基、3-硝基酪氨酸和丙二醛）呈负相关，但在GO受试者中没有。总之，我们的结果支持这样一个假设，即与普通人群相比，百岁老人后代的PBMC对锌的反应减弱，这是由于锌稳态的更严格控制，这可能为他们在整个寿命期间提供持续的应激刺激保护。

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