Abstract：
In aging, the organism is unable to counteract certain harmful influences over its lifetime which leads to progressive dysfunction and eventually death, thus delineating aging as one failed process of adaptation to a set of aging stimuli. A central problem in understanding aging is hence to explain why the organism cannot adapt to these aging stimuli. The adaptation-maladaptation theory of aging proposes that in aging adaptation processes such as adaptive transcription, epigenetic remodeling, and metabolic plasticity drive dysfunction themselves over time (maladaptation) and thereby cause aging-related disorders such as cancer and metabolic dysregulation. The central dilemma of aging is thus that the set of adaptation mechanisms that the body uses to deal with internal and external stressors acts as a stressor itself and cannot be effectively counteracted. The only available option for the organism to decrease maladaptation may be a program to progressively reduce the output of adaptive cascades (e.g., via genomic methylation) which then leads to reduced physiological adaptation capacity and syndromes like frailty, immunosenescence, and cognitive decline. The adaptation-maladaptation dilemma of aging entails that certain biological mechanisms can simultaneously protect against aging as well as drive aging. The key to longevity may lie in uncoupling adaptation from maladaptation.
摘要：
在衰老中，生物体在其一生中无法抵消某些有害影响，从而导致进行性功能障碍并最终死亡，因此，将衰老描述为适应一组衰老刺激的失败过程。因此，理解衰老的一个核心问题是解释为什么生物体不能适应这些衰老刺激。衰老的适应-适应不良理论提出，在衰老适应过程中，如适应性转录，表观遗传重塑，和代谢可塑性驱动功能障碍本身随着时间的推移（不适应），从而导致衰老相关的疾病，如癌症和代谢失调。因此，衰老的核心困境是，身体用来应对内部和外部压力源的一套适应机制本身就是压力源，无法有效抵消。有机体减少适应不良的唯一可用选择可能是逐步减少自适应级联输出的程序（例如，通过基因组甲基化），然后导致生理适应能力降低和虚弱等综合征，免疫衰老，和认知能力下降。衰老的适应-适应不良困境意味着某些生物机制可以同时防止衰老和驱动衰老。长寿的关键可能在于将适应与不良适应解耦。
