An emerging role for cysteine-mediated redox signaling in aging

Reactive oxygen species (ROS) and hydrogen sulfide (H₂S) are naturally produced during metabolic processes. At physiological levels, they act as oxidation-reduction (redox) signaling molecules and regulate a myriad of cellular processes. Redox signaling occurs largely through rapid and reversible oxidation of reactive cysteine residues in target proteins, leading to changes in protein ligand binding affinity, subcellular localization, and function. Recent studies have demonstrated that ROS and H₂S play an essential role in various longevity models, and that a mild increase in ROS or H₂S levels is sufficient to extend lifespan in model organisms. Meanwhile, the number of aging-related proteins that are modulated by ROS- or H₂S-mediated post-translational modification is constantly growing. In this review, we aim to summarize key results that support cysteine-based redox regulation of organismal aging and lifespan. Better understanding of how mechanistically redox signaling controls aging will provide new perspectives for the development of targeted anti-aging strategies.