Iron promotes protein insolubility and aging in C. elegans.
Iron promotes protein insolubility and aging in C. elegans.
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DOI：
10.18632/aging.100689
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发表时间：
2014-11
期刊：
影响因子：
--
通讯作者：
Lithgow GJ
中科院分区：
文献类型：
--
作者：
Klang IM;Schilling B;Sorensen DJ;Sahu AK;Kapahi P;Andersen JK;Swoboda P;Killilea DW;Gibson BW;Lithgow GJ
许多起病较晚的蛋白毒性疾病伴随着铁、铜和锌等金属的动态平衡的破坏。尽管衰老是这些疾病最突出的危险因素，但衰老对金属沉积的影响及其在蛋白毒性疾病中的作用仍然知之甚少。此外，目前还不清楚金属沉积的丧失是否会影响正常的衰老。我们研究了金属沉积在秀丽线虫寿命中的作用。我们发现，钙、铜、铁和锰的水平随着年龄的增长而增加，而钾和磷的水平则有下降的趋势。膳食铁的增加显著加速了与年龄相关的不溶性蛋白质的积累，这是衰老的一种分子病理。蛋白质组学分析表明，膳食铁在多种细胞器和组织中具有广泛的作用。阻止特定金属积累的药物干预可以减弱许多蛋白毒性模型，延长正常寿命。总而言之，这些结果表明，随着年龄的增长，金属沉积的丧失有助于与年龄相关的蛋白质聚集。
Many late-onset proteotoxic diseases are accompanied by a disruption in homeostasis of metals (metallostasis) including iron, copper and zinc. Although aging is the most prominent risk factor for these disorders, the impact of aging on metallostasis and its role in proteotoxic disease remain poorly understood. Moreover, it is not clear whether a loss of metallostasis influences normal aging. We have investigated the role of metallostasis in longevity of Caenorhabditis elegans. We found that calcium, copper, iron, and manganese levels increase as a function of age, while potassium and phosphorus levels tend to decrease. Increased dietary iron significantly accelerated the age-related accumulation of insoluble protein, a molecular pathology of aging. Proteomic analysis revealed widespread effects of dietary iron in multiple organelles and tissues. Pharmacological interventions to block accumulation of specific metals attenuated many models of proteotoxicity and extended normal lifespan. Collectively, these results suggest that a loss of metallostasis with aging contributes to age-related protein aggregation.
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