The meaning of adaptation in aging: insights from cellular senescence, epigenetic clocks and stem cell alterations.

With recent rapid progress in research on aging, there is increasing evidence that many features commonly considered to be mechanisms or drivers of aging in fact represent adaptations. Here, we examine several such features, including cellular senescence, epigenetic aging and stem cell alterations. We draw a distinction between the causes and consequences of aging and define short-term consequences as 'responses' and long-term ones as 'adaptations'. We also discuss 'damaging adaptations', which despite having beneficial effects in the short term, lead to exacerbation of the initial insult and acceleration of aging. Features commonly recognized as 'basic mechanisms of the aging process' are critically examined for the possibility of their adaptation-driven emergence from processes such as cell competition and the wound-like features of the aging body. Finally, we speculate on the meaning of these interactions for the aging process and their relevance for the development of antiaging interventions.