Healthy cells utilize a series of protein quality regulatory networks to maintain the integrity and functionality of their proteome, named as protein homeostasis (proteostasis). However, the phenomenon of proteostasis collapse, including the destruction of the balance between protein synthesis, folding and degradation, are common with aging. The main causes of age-associated proteostasis collapse are as follows: (1) the decline in transcriptional activation of stress response related pathways, (2) the reduction of proteasome and autophagy activity, and (3) ribosome pausing during translation. In addition, proteostasis is regulated mainly through chaperones, proteasomes, and autophagy systems of proteostasis network in aging. This paper mainly reviews the causes of age-associated proteostasis collapse and the pathways of proteostasis regulation, which may open the way to explore aging studies and solve aging problems.
健康细胞利用一系列蛋白质质量调控网络来维持自身蛋白质组的稳定性和功能性,即维持蛋白稳态。但是在衰老过程中普遍出现蛋白稳态失衡的现象,其主要表现是蛋白质合成、折叠和降解之间的平衡被破坏。造成衰老相关蛋白稳态失衡的原因主要有：(1)应激反应相关途径的转录受到抑制;(2)蛋白酶体活性降低和自噬功能出现障碍;(3)核糖体翻译暂停。另外,在衰老过程中细胞主要通过蛋白稳态网络的分子伴侣、蛋白酶体、自噬系统等对蛋白稳态进行调节。本文对衰老过程中造成蛋白稳态失衡的诱因以及蛋白稳态调控的途径进行综述,以期为衰老研究和解决老年健康问题开拓新思路。.
Keywords: aging; proteostasis collapse; proteostasis network.