Hormesis: What it is and why it matters

Abstract

Hormesis describes any process in which a cell, organism, or group of organisms exhibits a biphasic response to exposure to increasing amounts of a substance or condition (e.g., chemical, sensory stimulus, or metabolic stress); typically, low-dose exposures elicit a stimulatory or beneficial response, whereas high doses cause inhibition or toxicity. The biphasic dose-response signature of hormesis is a common result of experiments in the field of toxicology, but the low-dose data have been largely ignored, and the prevailing view is that it is important to reduce levels of toxins as much as possible. However, in many cases, the toxins actually have essential or beneficial effects in low amounts. Prominent examples of such beneficial toxins are trace metals such as selenium, chromium, and zinc. Fundamental inter- and intracellular signals also exhibit hormetic dose responses, including hormones, neurotransmitters, growth factors, calcium, and protein kinases. Moreover, everyday health-promoting lifestyle factors, including exercise and dietary energy restriction, act, at least in part, through hormetic mechanisms involving activation of adaptive cellular stress response pathways (ACSRPs). ACSRPs typically involve receptors coupled to kinases and activation of transcription factors that induce the expression of cytoprotective proteins such as antioxidant enzymes, protein chaperones, and growth factors. The recognition and experimental utilization of hormesis is leading to novel approaches for preventing and treating a range of diseases, including cancers, cardiovascular disease, and neurodegenerative disorders.