Department of Biomedical Science, Graduate School, Kyungpook National University, Daegu, Republic of Korea; BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Republic of Korea.
Department of Preventative Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
Environ Pollut. 2018 Feb;233:725-734. doi: 10.1016/j.envpol.2017.10.124. Epub 2017 Nov 7.
Although the toxicity of synthetic chemicals at high doses is well known, chronic exposure to low-dose chemical mixtures has only recently been linked to many age-related diseases. However, it is nearly impossible to avoid the exposure to these low-dose chemical mixtures as humans are exposed to a myriad of synthetic chemicals as a part of their daily lives. Therefore, coping with possible harms due to low dose chemical mixtures is challenging. Interestingly, within the range of environmental exposure, disease risk does not increase linearly with increasing dose of chemicals, but often tends to plateau or even decrease with increasing dose. Hormesis, the over-compensation of various adaptive responses through cellular stresses, is one possible mechanism for this non-linearity. Although the hormetic effects of synthetic chemicals or radiation have long been debated in the field of toxicology, the hormesis concept has recently been generalized in the field of molecular biology; similar to responses to synthetic chemicals, mild to moderate intermittent stressors from any source can induce hormetic responses. Examples of stressors are exercise, calorie restriction, intermittent fasting, cognitive stimulation, and phytochemicals. Mitohormesis is hormesis induced by such stressors through mitochondrial retrograde signalling including the increased production of mild reactive oxygen species. Xenohormesis is phytochemical-induced hormesis, reflective of a mutualistic relationship between plant and animals. As humans had repeated exposure to all of these stressors during their evolution, the hormetic effects of these health behaviours may be considered to be evolutionarily adapted. Although hormesis induced by synthetic chemicals occurs in humans, such hormesis may not be recommended to the public due to unresolved issues on safety including the impossibility of control exposure. However, the use of personal health behaviors which enhance mitohormetic- or xenohormetic-stress can be readily incorporated into everyone's daily lives as a practical way to counteract harmful effects of unavoidable low-dose chemical mixtures.
虽然高剂量合成化学物质的毒性是众所周知的,但最近才发现慢性低剂量化学混合物暴露与许多与年龄相关的疾病有关。然而,由于人类在日常生活中会接触到无数种合成化学物质,因此几乎不可能避免接触这些低剂量化学混合物。因此,应对低剂量化学混合物可能造成的危害具有挑战性。有趣的是,在环境暴露范围内,疾病风险不会随化学物质剂量的增加而线性增加,而是往往随着剂量的增加而趋于平稳甚至下降。适应细胞应激的各种适应性反应的过度补偿是这种非线性的一种可能机制。尽管合成化学物质或辐射的赫姆氏效应在毒理学领域长期存在争议,但近年来这一概念在分子生物学领域得到了推广;类似于对合成化学物质的反应,温和到中等强度的间歇性应激源(来自任何来源)都可以诱导赫姆氏反应。应激源的例子包括运动、热量限制、间歇性禁食、认知刺激和植物化学物质。通过包括轻度活性氧产生在内的线粒体逆行信号,这些应激源诱导的mitohormesis。xenohormesis 是植物化学物质诱导的赫姆氏效应,反映了植物和动物之间的共生关系。由于人类在进化过程中反复接触所有这些应激源,这些健康行为的赫姆氏效应可能被认为是进化适应的。尽管人类会发生由合成化学物质引起的赫姆氏效应,但由于包括无法控制暴露在内的安全问题尚未解决,这种赫姆氏效应可能不被推荐给公众。然而,增强 mitohormetic-或 xenohormetic-应激的个人健康行为可以很容易地融入每个人的日常生活中,作为应对不可避免的低剂量化学混合物有害影响的一种实用方法。