Oxidative stress in chronic disease: Mechanisms, therapeutic strategies, and future directions

Oxidative stress, resulting from an imbalance between reactive oxygen species (ROS) and endogenous antioxidant defenses, is a central driver of numerous chronic diseases. While ROS are essential for physiological signaling, their excessive accumulation damages cellular macromolecules, promotes inflammation, and accelerates tissue dysfunction and aging. Conventional antioxidant therapies have yielded inconsistent clinical benefits, reflecting the dual role of ROS in health and disease. This review examines the mechanisms of ROS generation, the role of Nrf2 in maintaining redox homeostasis, and the contribution of oxidative stress to conditions such as neurodegeneration, cardiovascular disorders, chronic obstructive pulmonary disease, and cancer. We also discuss emerging therapeutic strategies, including mitochondria-targeted antioxidants, nanotechnology-based delivery systems, gene therapy, epigenetic modulation, and microbiome–redox interactions. By integrating mechanistic insights with precision-based approaches, these interventions offer promising avenues for restoring redox balance and improving outcomes in chronic disease management.