Department of Molecular Biology and Genetics, Laboratory of Cellular Ageing, Aarhus University, Gustav Wieds Vej 10C, Aarhus C, Denmark.
Expert Opin Drug Discov. 2012 May;7(5):439-48. doi: 10.1517/17460441.2012.677430. Epub 2012 Apr 17.
Mild stress-induced hormesis is becoming increasingly attractive as an ageing interventional strategy and is leading to the discovery of hormesis-inducing compounds called hormetins. Almost 50 years of modern biogerontolgical research has established a clear framework regarding the biological basis of ageing and longevity, and it is now generally accepted that ageing occurs in spite of the presence of complex pathways of maintenance, repair and defense, and there is no 'enemy within.' This viewpoint makes modulation of ageing different from the treatment of one or more age-related diseases. A promising strategy to slow down ageing and prevent or delay the onset of age-related diseases is that of mild stress-induced hormesis by using hormetins.
The article presents the rationale and a strategy for discovering novel hormetins as potential drugs for ageing intervention by elucidating multiple stress responses of normal human cells. Furthermore, it discusses the first steps in identifying prospective hormetin drugs and provides a recent example of successful product development, based on the ideas of hormesis and by following the strategy described here.
As a biomedical issue, the biological process of ageing underlies several major diseases, and although the optimal treatment of every disease, irrespective of age, is a social and moral necessity, preventing the onset of age-related diseases by intervening in the basic process of ageing is the best approach for achieving healthy ageing and for extending the healthspan.
轻度应激诱导的有益效应作为一种衰老干预策略变得越来越有吸引力,并导致了有益效应诱导化合物(称为有益效应素)的发现。近 50 年的现代生物老年学研究已经建立了一个关于衰老和长寿的生物学基础的明确框架,现在人们普遍认为,尽管存在复杂的维持、修复和防御途径,但衰老还是会发生,而且体内没有“敌人”。这种观点使得衰老的调控与一种或多种与年龄相关的疾病的治疗不同。一种有前途的减缓衰老和预防或延迟与年龄相关的疾病发作的策略是使用有益效应素来诱导轻度应激诱导的有益效应。
本文提出了通过阐明正常人类细胞的多种应激反应来发现新的有益效应素作为潜在的衰老干预药物的原理和策略。此外,它讨论了确定潜在有益效应素药物的第一步,并提供了一个基于有益效应的思想和遵循这里描述的策略的成功产品开发的最近例子。
作为一个生物医学问题,衰老的生物学过程是几种主要疾病的基础,尽管无论年龄大小,对每种疾病的最佳治疗都是一种社会和道德的需要,但通过干预衰老的基本过程来预防与年龄相关的疾病是实现健康衰老和延长健康寿命的最佳方法。