16. Is oxidative damage a cause of aging?

Oxidative damage is measurable, and sometimes consequential, but it is not sufficient as a general cause of aging, and treating it as the explanation has repeatedly failed to generalize. Reactive oxygen species (ROS) are prototypical by-products of metabolism and other cellular processes, but they are only one instance of a broader principle: because every biological process is imperfect, life inevitably generates many classes of mildly deleterious by-products and errors, and aging reflects the net accumulation of this heterogeneous burden (the deleteriome), not one privileged damage type. The impact of oxidative lesions therefore depends on system architecture, i.e. where ROS are produced, what they hit, how effectively they are prevented/repaired/removed, and how the organism’s genotype and metabolic organization route resources between performance and maintenance. This framing also explains the empirical contradictions: boosting antioxidant defenses does not reliably extend lifespan across contexts, can be ineffective or even shorten lifespan in some settings, and aging can proceed even when oxygen/ROS are not the dominant constraint. In short, oxidative damage is one component of the deleteriome and an important window into biology, but it is not a universal driver; what matters is how oxidative damage, and all other damage forms, are integrated, buffered, and diluted/removed within the whole system.