The Buck Institute for Research on Aging, Novato, CA, USA.
Proteomics. 2018 Mar;18(5-6):e1700108. doi: 10.1002/pmic.201700108.
Progressive loss of proteostasis is a hallmark of aging that is marked by declines in various components of proteostasis machinery, including: autophagy, ubiquitin-mediated degradation, protein synthesis, and others. While declines in proteostasis have historically been observed as changes in these processes, or as bulk changes in the proteome, recent advances in proteomic methodologies have enabled the comprehensive measurement of turnover directly at the level of individual proteins in vivo. These methods, which utilize a combination of stable-isotope labeling, mass spectrometry, and specialized software analysis, have now been applied to various studies of aging and longevity. Here we review the role of proteostasis in aging and longevity, with a focus on the proteomic methods available to conduct protein turnover in aging models and the insights these studies have provided thus far.
进行性蛋白质稳态丧失是衰老的一个标志,其特征是蛋白质稳态机制的各种成分下降,包括:自噬、泛素介导的降解、蛋白质合成等。虽然蛋白质稳态的下降在历史上一直被观察为这些过程的变化,或者是蛋白质组的整体变化,但蛋白质组学方法的最新进展使得能够在体内直接对单个蛋白质的周转率进行全面测量。这些方法结合了稳定同位素标记、质谱和专门的软件分析,现已应用于各种衰老和长寿的研究。在这里,我们回顾了蛋白质稳态在衰老和长寿中的作用,重点介绍了可用于衰老模型中进行蛋白质周转率的蛋白质组学方法,以及这些研究迄今为止提供的见解。