Redox Regulation of Complement Pathway Activation in Aging and Related Diseases

Aging is a complex degenerative process characterized by the accumulation of molecular damage and a heightened susceptibility to disease. The oxidative stress theory of aging identifies endogenous reactive oxygen species (ROS) as primary drivers of this cellular deterioration. This review provides a comprehensive analysis of the critical, yet underappreciated, interplay between oxidative stress and the complement system, a powerful effector of innate immunity. We detail the mechanistic pathways through which redox imbalance directly activates complement components and, conversely, how complement activation amplifies oxidative stress, creating a vicious cycle that accelerates tissue damage. A central focus is placed on how this redox-complement axis contributes to the pathophysiology of age-related conditions, including neurodegenerative, cardiovascular, and metabolic diseases. Furthermore, the review explores emerging therapeutic strategies that target this interaction, highlighting the potential of antioxidant and complement-inhibitory approaches to disrupt this cycle and promote healthy aging. By synthesizing current evidence, this work underscores the significance of the redox-complement network as a key mechanistic link in aging and its associated diseases.