遗传 ›› 2022, Vol. 44 ›› Issue (9): 733-744.doi: 10.16288/j.yczz.22-126

• 综述 • 上一篇    下一篇

衰老相关的蛋白稳态失衡

黎嘉丽(), 李瑾(), 汪虎()   

  1. 杭州师范大学基础医学院衰老研究所,浙江省衰老与癌变重点实验室,杭州 311121
  • 收稿日期:2022-04-26 修回日期:2022-06-28 出版日期:2022-09-20 发布日期:2022-07-27
  • 通讯作者: 李瑾,汪虎 E-mail:lijiali_carry@163.com;lijin@hznu.edu.cn;20120066@hznu.edu.cn
  • 作者简介:黎嘉丽,在读硕士研究生,专业方向:细胞生物学。E-mail: lijiali_carry@163.com
  • 基金资助:
    国家重点研发计划编号(2018YFA0109300);国家重点研发计划编号(2021YFA1102800);国家自然科学基金优青项目(编号)(82022026);广东省自然科学基金-杰出青年项目(编号)(2019B151502008);浙江省自然科学基金探索项目(编号)资助(LQ22H250001)

Age-associated proteostasis collapse

Jiali Li(), Jin Li(), Hu Wang()   

  1. Key Laboratory of Ageing and Cancer Biology of Zhejiang Province, Institute of Ageing Research, Hangzhou Normal Universtiy School of Medicine, Hangzhou 311121, China
  • Received:2022-04-26 Revised:2022-06-28 Online:2022-09-20 Published:2022-07-27
  • Contact: Li Jin,Wang Hu E-mail:lijiali_carry@163.com;lijin@hznu.edu.cn;20120066@hznu.edu.cn
  • Supported by:
    Supported by the National Key Research and Development Program of China Nos(2018YFA0109300);Supported by the National Key Research and Development Program of China Nos(2021YFA1102800);the National Natural Science Fund for Excellent Young Scholars No(82022026);the Science Foundation for Distinguished Young Scholars of Guangdong Province No(2019B151502008);the Natural Science Foundation of Zhejiang Province No(LQ22H250001)

摘要:

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。

关键词: 衰老, 蛋白稳态失衡, 蛋白稳态网络

Abstract:

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.

Key words: aging, proteostasis collapse, proteostasis network