Zinc Levels Modulate Lifespan through Multiple Longevity Pathways in Caenorhabditis elegans.
Zinc Levels Modulate Lifespan through Multiple Longevity Pathways in Caenorhabditis elegans.
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DOI：
10.1371/journal.pone.0153513
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Kapahi P
中科院分区：
文献类型：
--
作者：
Kumar J;Barhydt T;Awasthi A;Lithgow GJ;Killilea DW;Kapahi P
锌是一种必需的痕量金属，在许多生物过程中发挥着不可或缺的作用，包括酶功能、蛋白质结构和细胞信号通路。锌的过量和缺乏都会对发育和新陈代谢产生不利影响，导致畸形和疾病。我们改变了秀丽隐杆线虫体内的锌平衡，以检验锌负荷的变化如何影响无脊椎动物模型的寿命和健康寿命。我们发现，体内锌水平的增加与过量的膳食锌补充降低了线虫的平均和最长寿命，而通过锌选择性螯合剂降低体内的锌水平则延长了线虫的平均和最长寿命。我们确定，过量锌的寿命缩短效应需要DAF-16、HSF-1和SKN-1蛋白的表达，而减少锌的寿命延长效应可能部分依赖于这一组蛋白质。此外，与对照组相比，降低锌水平导致DAF-16更多的核定位和更多的Dauer形成，这表明锌的寿命效应部分是通过胰岛素/IGF-1途径介导的。此外，锌的状态与蠕虫健康寿命的几个标志有关，包括蛋白质平衡、运动和耐热性，锌水平的降低总是与功能的改善有关。综上所述，这些数据支持锌在调节线虫发育和寿命方面的作用，这表明对线虫体内锌稳态的调节可能是拮抗多效性的一个例子。
Zinc is an essential trace metal that has integral roles in numerous biological processes, including enzymatic function, protein structure, and cell signaling pathways. Both excess and deficiency of zinc can lead to detrimental effects on development and metabolism, resulting in abnormalities and disease. We altered the zinc balance within Caenorhabditis elegans to examine how changes in zinc burden affect longevity and healthspan in an invertebrate animal model. We found that increasing zinc levels in vivo with excess dietary zinc supplementation decreased the mean and maximum lifespan, whereas reducing zinc levels in vivo with a zinc-selective chelator increased the mean and maximum lifespan in C. elegans. We determined that the lifespan shortening effects of excess zinc required expression of DAF-16, HSF-1 and SKN-1 proteins, whereas the lifespan lengthening effects of the reduced zinc may be partially dependent upon this set of proteins. Furthermore, reducing zinc levels led to greater nuclear localization of DAF-16 and enhanced dauer formation compared to controls, suggesting that the lifespan effects of zinc are mediated in part by the insulin/IGF-1 pathway. Additionally, zinc status correlated with several markers of healthspan in worms, including proteostasis, locomotion and thermotolerance, with reduced zinc levels always associated with improvements in function. Taken together, these data support a role for zinc in regulating both development and lifespan in C. elegans, and that suggest that regulation of zinc homeostasis in the worm may be an example of antagonistic pleiotropy.