Aging's competing paradigms: Another decade of investigation into damage-driven versus programmed theories

The nature of aging remains debated: is it the accumulation of damage or by execution of a program? Here, we revisit this long-standing dichotomy in light of recent experimental advances, each one of us supporting one of those paradigms and being critical about the other. The damage-driven model views aging as the progressive loss of function caused by imperfect repair and modulated by factors such as rate of damage accumulation, damage resistance, biological redundancy, and tissue regeneration. In contrast, the discussed program-driven framework argues that aging evolved as a genetic program. By presenting both models side by side, we outline testable hypotheses to determine which one is more accurate. Resolving whether aging stems chiefly from damage accumulation or adaptive programming will shape the trajectory of geroscience and the design of therapeutic interventions aimed at extending healthy lifespan.