Biomedical Research Institute of Lleida (IRBLLEIDA) - +Pec Proteomics Research Group (+PPRG) - Neuroscience Area - University Hospital Arnau de Vilanova (HUAV), Lleida, 25198, Spain.
Department of Medical Basic Sciences, University of Lleida (UdL), Lleida, 25198, Spain.
Aging (Albany NY). 2024 Jul 25;16(15):11484-11490. doi: 10.18632/aging.206036.
Increased oxidative stress (OS) and the disruption of the equilibrium between the production of reactive oxygen species and antioxidants are key molecular features of unhealthy aging. OS results in the formation of oxidative posttranslational modifications (PTMs), some of which involve cysteine (Cys) residues in aging proteomes, and specifically, the formation of trioxidized Cys (t-Cys), which leads to permanent protein damage. Recent findings in rodents have uncovered that irregular regulation of t-Cys residues in the aging proteome disrupts homeostatic phosphorylation signaling, resulting in alterations to proteins that are analogous to those caused by phosphorylated serine (p-Ser) residues. This work contextualizes these significant findings and discusses the implications and molecular role(s) of t-Cys in the aging proteome. Furthermore, we present novel data, validating the increase of specific t-Cys sites associated with aging in a blood-related circulating human proteome. The scope and findings included here support the hypothesis that t-Cys residues may serve as important mechanistic and biological markers, warranting further exploration in the context of unhealthy aging and age-related major diseases.
氧化应激（OS）的增加和活性氧物质产生与抗氧化剂之间平衡的破坏是不健康衰老的关键分子特征。OS 导致氧化翻译后修饰（PTM）的形成，其中一些涉及衰老蛋白质组中的半胱氨酸（Cys）残基，特别是三氧化 Cys（t-Cys）的形成，导致蛋白质的永久性损伤。最近在啮齿动物中的发现揭示了衰老蛋白质组中 t-Cys 残基的不规则调节会破坏稳态磷酸化信号，导致类似于磷酸化丝氨酸（p-Ser）残基引起的蛋白质改变。这项工作将这些重要发现置于上下文中，并讨论了 t-Cys 在衰老蛋白质组中的意义和分子作用。此外，我们还提供了新的数据，验证了与血液相关的循环人类蛋白质组中与衰老相关的特定 t-Cys 位点的增加。这里包含的范围和发现支持了 t-Cys 残基可能作为重要的机制和生物学标志物的假设，值得在不健康衰老和与年龄相关的重大疾病的背景下进一步探索。
