Evolutionarily adapted hormesis-inducing stressors can be a practical solution to mitigate harmful effects of chronic exposure to low dose chemical mixtures

Abstract

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.

Keywords: Chemical mixtures; Hormesis; Mitohormesis; Non-monotonic dose response relation; Persistent organic pollutants; Xenohormesis.