The decay of Redox-stress Response Capacity is a substantive characteristic of aging: Revising the redox theory of aging.
The decay of Redox-stress Response Capacity is a substantive characteristic of aging: Revising the redox theory of aging.
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氧化还原应激反应能力的衰减是衰老的本质特征：对衰老氧化还原理论的修正
DOI：
10.1016/j.redox.2016.12.026
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发表时间：
2017-04
期刊：
影响因子：
11.4
通讯作者：
Chen, Chang
中科院分区：
文献类型：
--
作者：
Meng, Jiao;Lv, Zhenyu;Qiao, Xinhua;Li, Xiaopeng;Li, Yazi;Zhang, Yuying;Chen, Chang
衰老与氧化还原事件密切相关。自由基衰老理论表明氧化还原失衡可能是衰老过程中的一个重要因素。大多数关于氧化还原和衰老的研究都集中在氧化应激水平的静态状态上，很少有关于衰老过程中氧化还原挑战的差异反应的研究。在这项研究中，我们使用秀丽隐杆线虫和人类成纤维细胞作为模型来比较年轻人和老年人对氧化应激挑战的不同反应。在百草枯胁迫下，年轻个体产生了更多的ROS，激活了包括p-ERK、p-AKT和p-AMPKα/β在内的信号通路。在初始反应后，年轻个体随后促进NRF2易位，诱导额外的抗氧化酶和更高的II期酶表达，包括SOD、CAT、GPX、HO-1、gstp -1等，以维持氧化还原稳态。此外，通过上调伴侣蛋白的表达和提高蛋白酶体的活性，年轻个体也表现出更好的降解受损蛋白的能力。基于这些数据，我们提出了一个新的概念“氧化还原-应激反应能力（RRC）”，这表明细胞或生物体能够产生动态氧化还原反应来激活细胞信号传导并维持细胞稳态。RRC的衰变是老化的实质特征，对氧化还原老化理论有了新的认识。
Aging is tightly associated with redox events. The free radical theory of aging indicates that redox imbalance may be an important factor in the aging process. Most studies about redox and aging focused on the static status of oxidative stress levels, there has been little research investigating differential responses to redox challenge during aging. In this study, we used Caenorhabditis elegans and human fibroblasts as models to compare differential responses to oxidative stress challenge in young and old individuals. In response to paraquat stress, young individuals generated more ROS and activated signaling pathways including p-ERK, p-AKT and p-AMPKα/β. After the initial response, young individuals then promoted NRF2 translocation and induced additional antioxidant enzymes and higher expression of phase II enzymes, including SOD, CAT, GPX, HO-1, GSTP-1and others, to maintain redox homeostasis. Moreover, young individuals also demonstrated a better ability to degrade damaged proteins by up-regulating the expression of chaperones and improving proteasome activity. Based on these data, we propose a new concept "Redox-stress Response Capacity (RRC)", which suggests cells or organisms are capable of generating dynamic redox responses to activate cellular signaling and maintain cellular homeostasis. The decay of RRC is the substantive characteristic of aging, which gives a new understand of the redox theory of aging.
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