Protein Turnover in Aging and Longevity

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.