Calabrese Edward J, Osakabe Naomi, Di Paola Rosanna, Siracusa Rosalba, Fusco Roberta, D'Amico Ramona, Impellizzeri Daniela, Cuzzocrea Salvatore, Fritsch Tilman, Abdelhameed Ali S, Wenzel Uwe, Franceschi Claudio, Calabrese Vittorio
Department of Environmental Health Sciences, Morrill I, N344, University of Massachusetts, Amherst, MA 01003, USA.
Department of Bioscience and Engineering, Shibaura Institute Technology, Tokyo, Japan.
Ageing Res Rev. 2023 Nov;91:102074. doi: 10.1016/j.arr.2023.102074. Epub 2023 Sep 13.
This commentary provides a novel synthesis of how biological systems adapt to a broad spectrum of environmental and age-related stresses that are underlying causes of numerous degenerative diseases and debilitating effects of aging. It proposes that the most fundamental, evolutionary-based integrative strategy to sustain and protect health is based on the concept of hormesis. This concept integrates anti-oxidant, anti-inflammatory and cellular repair responses at all levels of biological organization (i.e., cell, organ and organism) within the framework of biphasic dose responses that describe the quantitative limits of biological plasticity in all cells and organisms from bacteria and plants to humans. A major feature of the hormetic concept is that low levels of biological, chemical, physical and psychological stress upregulate adaptive responses that not only precondition, repair and restore normal functions to damaged tissues/organs but modestly overcompensate, reducing ongoing background damage, thereby enhancing health beyond that in control groups, lacking the low level "beneficial" stress. Higher doses of such stress often become counterproductive and eventually harmful. Hormesis is active throughout the life-cycle and can be diminished by aging processes affecting the onset and severity of debilitating conditions/diseases, especially in elderly subjects. The most significant feature of the hormetic dose response is that the limits of biological plasticity for adaptive processes are less than twice that of control group responses, with most, at maximum, being 30-60 % greater than control group values. Yet, these modest increases can make the difference between health or disease and living or dying. The quantitative features of these adaptive hormetic dose responses are also independent of mechanism. These features of the hormetic dose response determine the capacity to which systems can adapt/be protected, the extent to which biological performance (e.g., memory, resistance to injury/disease, wound healing, hair growth or lifespan) can be enhanced/extended and the extent to which synergistic interactions may occur. Hormesis defines the quantitative rules within which adaptive processes operate and is central to evolution and biology and should become transformational for experimental concepts and study design strategies, public health practices and a vast range of therapeutic strategies and interventions.
本评论对生物系统如何适应广泛的环境和与年龄相关的压力进行了新颖的综合阐述，这些压力是众多退行性疾病和衰老衰弱效应的根本原因。它提出，基于进化的维持和保护健康的最基本综合策略基于应激适应的概念。这一概念在双相剂量反应的框架内，整合了生物组织各级（即细胞、器官和生物体）的抗氧化、抗炎和细胞修复反应，该框架描述了从细菌、植物到人类的所有细胞和生物体中生物可塑性的定量极限。应激适应概念的一个主要特征是，低水平的生物、化学、物理和心理压力会上调适应性反应，这些反应不仅为受损组织/器官预处理、修复并恢复正常功能，还会适度过度补偿，减少持续的背景损伤，从而使健康状况优于未经历低水平“有益”压力的对照组。更高剂量的此类压力往往会适得其反，最终造成伤害。应激适应在整个生命周期中都很活跃，并且会因影响衰弱状况/疾病的发生和严重程度的衰老过程而减弱，尤其是在老年受试者中。应激适应剂量反应的最重要特征是，适应性过程的生物可塑性极限小于对照组反应极限的两倍，大多数情况下，最大比对照组值高30 - 60%。然而，这些适度的增加可能决定健康与疾病、生存与死亡的差异。这些适应性应激适应剂量反应的定量特征也与机制无关。应激适应剂量反应的这些特征决定了系统能够适应/得到保护的能力、生物性能（如记忆、对损伤/疾病的抵抗力、伤口愈合、头发生长或寿命）能够增强/延长的程度以及协同相互作用可能发生的程度。应激适应定义了适应性过程运作的定量规则，是进化和生物学的核心，并且应该对实验概念和研究设计策略、公共卫生实践以及众多治疗策略和干预措施产生变革性影响。
