Pace Marta, Giorgi Chiara, Lombardozzi Giorgia, Cimini Annamaria, Castelli Vanessa, d'Angelo Michele
Department of Life, Health and Environmental Sciences, University of L'Aquila, 67100 L'Aquila, Italy.
Sbarro Institute for Cancer Research and Molecular Medicine, Temple University, Philadelphia, PA 19122, USA.
Biomolecules. 2025 Aug 3;15(8):1115. doi: 10.3390/biom15081115.
Aging is a complex, universal biological process characterized by the progressive and irreversible decline of physiological functions across multiple organ systems. This deterioration is primarily driven by cumulative cellular damage arising from both intrinsic and extrinsic stressors. The free radical theory of aging, first proposed by Denham Harman in 1956, highlights the role of reactive oxygen species (ROS), byproducts of normal metabolism, in driving oxidative stress and age-related degeneration. Emerging evidence emphasizes the importance of redox imbalance in the onset of neurodegenerative diseases and aging. Among the critical cellular defenses against oxidative stress are sulfur-containing amino acids, namely cysteine (Cys) and selenocysteine (Sec). Cysteine serves as a precursor for glutathione (GSH), a central intracellular antioxidant, while selenocysteine is incorporated into key antioxidant enzymes such as glutathione peroxidases (GPx) and thioredoxin reductases (TrxR). These molecules play pivotal roles in neutralizing ROS and maintaining redox homeostasis. This review aims to provide an updated and critical overview of the role of thiol-containing amino acids, specifically cysteine and selenocysteine, in the regulation of redox homeostasis during aging.
衰老 是一个复杂的、普遍存在的生物学过程，其特征是多个器官系统的生理功能进行性且不可逆地衰退。这种衰退主要由内在和外在应激源引起的累积性细胞损伤驱动。1956年由德纳姆·哈曼首次提出的衰老自由基理论，强调了正常代谢副产物活性氧（ROS）在引发氧化应激和与年龄相关的退化中的作用。新出现的证据强调了氧化还原失衡在神经退行性疾病和衰老发生中的重要性。含硫氨基酸，即半胱氨酸（Cys）和硒代半胱氨酸（Sec），是对抗氧化应激的关键细胞防御物质。半胱氨酸是细胞内主要抗氧化剂谷胱甘肽（GSH）的前体，而硒代半胱氨酸则被纳入关键的抗氧化酶中，如谷胱甘肽过氧化物酶（GPx）和硫氧还蛋白还原酶（TrxR）。这些分子在中和ROS和维持氧化还原稳态中起关键作用。本综述旨在提供关于含硫氨基酸，特别是半胱氨酸和硒代半胱氨酸，在衰老过程中氧化还原稳态调节作用的最新且批判性概述。
