Avoidance of rejuvenation: a stress test for evolutionary theories of aging

The biological feasibility of human rejuvenation remains a subject of intense debate, yet answering this question is critical for guiding research strategies. Should aging research focus only on reversing aging in older individuals, or pausing its progression at mid-ages, be more accessible? Here, we attempt to address this question with evolutionary biology. Rejuvenation occurs in a few species, and, paradoxically, is typically induced by stress but not used under optimal conditions. Using mathematical modeling of lifespan plasticity in eusocial insects that can rejuvenate, we show that avoidance of rejuvenation is poorly explained by classic theories of aging in their standard formulations, requiring substantial assumptions to fit them. By contrast, one of the programmed theories of aging-the pathogen control hypothesis-offers a consistent evolutionary framework for understanding avoidance of rejuvenation. Moreover, our model mathematically predicts the evolution of the genetic program executing lifespan termination - adaptive aging mechanisms.