Environmental hormesis and its fundamental biological basis: Rewriting the history of toxicology

Highlights: • Autophagy is activated in the framework of hormesis. • Low doses of stressors promote health and extend lifespan. • Health can be maximized via calorie restriction and intermittent fasting. • Hormesis can protect against aging diseases and exogenous environmental stresses. • Hormesis provides a perspective for enhancing community health and patient success. It has long been debated whether a little stress may be "good" for you. Extensive evidence has now sufficiently accumulated demonstrating that low doses of a vast range of chemical and physical agents induce protective/beneficial effects while the opposite occurs at higher doses, a phenomenon known as hormesis. Low doses of environmental agents have recently induced autophagy, a critical adaptive response that protects essentially all cell types, as well as being transgenerational via epigenetic mechanisms. These collective findings highlight a generalized and substantial ongoing dose-response transformation with significant implications for disease biology and clinical applications, challenging the history and practice of toxicology and pharmacology along with an appeal to stake holders to reexamine the process of risk assessment, with the goal of optimizing public health rather than simply avoiding harm.