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 on reversing aging in older individuals, or on pausing its progression at earlier ages? We address this question with evolutionary biology.Classic evolutionary theories of aging— damage accumulation, antagonistic pleiotropy, and the disposable soma—consider aging as a detrimental byproduct of evolution. From this perspective, rejuvenation should confer substantial fitness advantages and therefore be expected to evolve in species experiencing aging in the wild. The rarity of rejuvenation in nature should thus be interpreted as evidence of its mechanistic implausibility.Yet, rejuvenation does occur 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, we show that avoidance of rejuvenation cannot be reconciled with classic theories of aging, revealing a fundamental contradiction between these theories and the observations. By contrast, the pathogen control hypothesis—which interprets aging as an adaptive, programmed process—offers a consistent evolutionary framework for understanding and potentially achieving rejuvenation. Moreover, our model mathematically predicts the evolution of the genetic program executing lifespan termination – an adaptive aging mechanism.