The Buck Institute for Research on Aging, Novato, CA, USA.
Proteomics. 2020 Mar;20(5-6):e1800403. doi: 10.1002/pmic.201800403. Epub 2019 Sep 10.
Aging and age-related diseases are accompanied by proteome remodeling and progressive declines in cellular machinery required to maintain protein homeostasis (proteostasis), such as autophagy, ubiquitin-mediated degradation, and protein synthesis. While many studies have focused on capturing changes in proteostasis, the identification of proteins that evade these cellular processes has recently emerged as an approach to studying the aging proteome. With advances in proteomic technology, it is possible to monitor protein half-lives and protein turnover at the level of individual proteins in vivo. For large-scale studies, these technologies typically include the use of stable isotope labeling coupled with MS and comprehensive assessment of protein turnover rates. Protein turnover studies have revealed groups of highly relevant long-lived proteins (LLPs), such as the nuclear pore complexes, extracellular matrix proteins, and protein aggregates. Here, the role of LLPs during aging and age-related diseases and the methods used to identify and quantify their changes are reviewed. The methods available to conduct studies of protein turnover, used in combination with traditional proteomic methods, will enable the field to perform studies in a systems biology context, as changes in proteostasis may not be revealed in studies that solely measure differential protein abundances.
衰老和与年龄相关的疾病伴随着蛋白质组重构和维持蛋白质平衡（蛋白质稳态）所需的细胞机制的逐渐衰退，如自噬、泛素介导的降解和蛋白质合成。虽然许多研究都集中在捕捉蛋白质稳态的变化上，但最近出现了一种研究衰老蛋白质组的方法，即识别逃避这些细胞过程的蛋白质。随着蛋白质组学技术的进步，有可能在体内单个蛋白质水平上监测蛋白质半衰期和蛋白质周转率。对于大规模研究，这些技术通常包括使用稳定同位素标记与 MS 结合以及全面评估蛋白质周转率。蛋白质周转率研究揭示了高度相关的长寿命蛋白（LLP）组，如核孔复合物、细胞外基质蛋白和蛋白聚集体。在这里，我们综述了 LLP 在衰老和与年龄相关的疾病中的作用，以及用于鉴定和量化它们变化的方法。可用于进行蛋白质周转率研究的方法与传统蛋白质组学方法相结合，将使该领域能够在系统生物学背景下进行研究，因为在仅测量差异蛋白质丰度的研究中可能不会揭示蛋白质稳态的变化。
