Age-associated proteostasis collapse.

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.