A Perspective on the Scientific, Philosophical, and Policy Dimensions of Hormesis

Abstract

The hormesis concept has broad implications for biology and the biomedical sciences. This perspective on hormesis concentrates on toxicology and toxicological risk assessment and secondarily explores observations from other fields. It considers the varied manifestations of hormesis in the context of a broad family of biological stress responses. Evidence for hormesis is reviewed, and the hormesis model is contrasted with more widely accepted dose-response models in toxicology: a linear nonthreshold (LNT) model for mutagenesis and carcinogenesis, and a threshold model for most other toxicologic effects. Scientific, philosophical, and political objections to the hormesis concept are explored, and complications in the hormesis concept are analyzed. The review concludes with a perspective on the current state of hormesis and challenges that the hormesis model poses for risk assessment.

New considerations on hormetic response against oxidative stress

“…As it has been also postulated that (Hoffmann 2009) the hormesis model runs counter to the assumption that effects at low doses can be predicted from those at high doses in a reasonably straightforward way. Nevertheless, when it comes to Nrf2 inductors and effects, the dose problem remains unsolved.…”

“…Hormesis can be defined as: "a process in which exposure to a low dose of a chemical agent or environmental factor that is damaging at higher doses induces an adaptive beneficial effect on the cell or organism" (Calabrese and Baldwin 2003;Calabrese 2008;Calabrese et al 2010;Mattson 2008;Rattan 2006;Hoffmann 2009) There have been many hormetic agents identified so far (Calabrese and Baldwin 2003;Le Bourg and Rattan 2009), however here we will only focus on the hormetic effect induced by oxidant compounds and inflammation. We will discuss three hormetic scenarios that we have been studying in the past few years.…”

Hormesis, Adaptive Epigenetic Reorganization, and Implications for Human Health and Longevity

“…On the other hand, aging is a complex process involving a persistent activation of some stress responsive systems, which can be consider a 'geroprotective' adaptation (Frolkis 1993). The hormetins [agents that induce hormesis (Hoffmann 2009)] can stimulate the self-maintenance and repair pathways, which increase adaptive abilities and thus delay senescence. Aging, rather than changes in individual cells, tissues, or organs, may be more a consequence of the deterioration of integrative mechanisms (Shock 1977).…”

Cellular Stress Responses, The Hormesis Paradigm, and Vitagenes: Novel Targets for Therapeutic Intervention in Neurodegenerative Disorders

“…Another issue that can affect clinical success is the nature of the dose response in and adjacent to the therapeutic zone (58,60). Over the past decade considerable advances have been made in the understanding of the nature of the dose response, especially in the low-dose zone (88,116,204,280,291,292,398). These findings challenge previous concepts of the dose response, suggesting that the commonly accepted threshold and linear doseresponse models upon which society has based its toxicological and pharmacological predications for drug and chemical effects often fail to provide reliable estimates of responses in the low-dose zone, that is, below the threshold (55, 61, 69-71, 90, 91).…”