Laboratory of Cellular Ageing, Department of Molecular Biology and Genetics, Aarhus University, Denmark.
Dose Response. 2013;11(1):99-108. doi: 10.2203/dose-response.11-054.Rattan. Epub 2012 Jan 12.
Application of hormesis in aging research and interventions is becoming increasingly attractive and successful. The reason for this is the realization that mild stress-induced activation of one or more stress response (SR) pathways, and its consequent stimulation of repair mechanisms, is effective in reducing the age-related accumulation of molecular damage. For example, repeated heat stress-induced synthesis of heat shock proteins has been shown to have a variety of anti-aging effects on growth and other cellular and biochemical characteristics of normal human skin fibroblasts, keratinocytes and endothelial cells undergoing aging in vitro. Therefore, searching for potential hormetins - conditions and compounds eliciting SR-mediated hormesis - is drawing attention of not only the researchers but also the industry involved in developing healthcare products, including nutriceuticals, functional foods and cosmeceuticals. Here we present the example of a skin care cosmetic as one of the first successful product developments incorporating the ideas of hormesis. This was based on the studies to analyse the molecular effects of active ingredients extracted from the roots of the Chinese herb Sanchi (Panax notoginseng) on gene expression at the level of mRNAs and proteins in human skin cells. The results showed that the ginsenosides extracted from Sanchi induced the transcription of stress genes and increased the synthesis of stress proteins, especially the heat shock protein HSP1A1 or Hsp70, in normal human keratinocytes and dermal fibroblasts. Furthermore, this extract also has significant positive effects against facial wrinkles and other symptoms of facial skin aging as tested clinically, which may be due to its hormetic mode of action by stress-induced synthesis of chaperones involved in protein repair and removal of abnormal proteins. Acceptance of such a hormesis-based product by the wider public could be instrumental in the social recognition of the concept of hormesis as the beneficial effects of mild stress of choice, and will encourage the development of novel health care products with physical, nutritional and mental hormetins.
应激激活效应在衰老研究和干预中的应用正变得越来越有吸引力和成功。其原因在于,人们意识到,轻度应激诱导的一种或多种应激反应(SR)途径的激活,及其随后对修复机制的刺激,可有效减少与年龄相关的分子损伤积累。例如,反复的热应激诱导热休克蛋白的合成,已被证明对体外衰老的正常人类皮肤成纤维细胞、角质形成细胞和内皮细胞的生长和其他细胞和生化特性具有多种抗衰老作用。因此,寻找潜在的应激素——引发 SR 介导的应激激活效应的条件和化合物——不仅引起了研究人员的关注,也引起了从事开发保健产品(包括营养保健品、功能性食品和化妆品)的行业的关注。在这里,我们以一种皮肤护理化妆品为例,展示了将应激激活效应的理念纳入其中的第一个成功产品开发案例。这是基于对从中国草药三七(Panax notoginseng)根部提取的活性成分对人皮肤细胞中 mRNA 和蛋白质水平的基因表达的分子作用的研究。结果表明,从三七中提取的人参皂苷诱导应激基因的转录,并增加应激蛋白的合成,特别是正常人类角质形成细胞和真皮成纤维细胞中的热休克蛋白 HSP1A1 或 Hsp70。此外,这种提取物在临床上也对脸部皱纹和其他皮肤老化症状具有显著的积极作用,这可能是由于其应激激活效应模式,通过应激诱导涉及蛋白质修复和去除异常蛋白质的伴侣蛋白的合成。更广泛的公众对这种基于应激激活效应的产品的接受,可能有助于社会认可应激激活效应作为一种有益的选择轻度应激的概念,并将鼓励开发具有物理、营养和精神应激素的新型保健产品。