Elucidating the Mechanism(s) of Hormesis at the Cellular Level: The Universal Cell Response

Abstract

Many environmental stressors elicit biphasic effects from single cells. Such cellular hormesis may be interpreted in terms of (a) the superimposition of simple biochemical processes or (b) the non-specific behaviour of the cell. The latter approach is emphasized in this article and identified with the universal cell response (UCR); however, the importance of identifying molecular-level concomitants of the UCR is also acknowledged. One difficulty is that when the dose of ligand is very low, mass-action assumptions become invalid and reliable analysis of receptor-ligand interactions requires knowledge of the binding mechanism; this difficulty is discussed. The UCR (cellular hormesis) and its possible underlying mechanisms are considered in the framework of a general scheme of cell life, which logically implies cellular homeostasis or homeorhesis. This framework may be particularly helpful for elucidating and perhaps quantifying conditioning hormesis (adaptation to stressors). The findings of studies on the UCR cannot be extrapolated unequivocally to hormesis in whole organisms or populations and cellular-level hormesis cannot be inferred from whole-organism hormesis. Nevertheless, it has been argued that a better understanding of the underlying cellular mechanisms, i.e., of the UCR, may facilitate the analysis of whole-organism and population data.

The challenge of evaluating health effects of organic food; operationalisation of a dynamic concept of health

“…metabolomics, proteomics, genomics), which might, in future times, allow for personalisation of the results obtained 14. The development of algorithms might help to circumvent these challenges 47. In any case, measurements need to be performed under well‐controlled circumstances, as health status (and its measurements) can be highly dependent on many factors.…”

Postconditioning Hormesis Put in Perspective: An Overview of Experimental and Clinical Studies

“…What these phenomena have in common is that their response relates biphasically to particular doses of stress. Such doseresponse relationships are qualitatively independent of the stress-inducing agent, the endpoint measured and the system under investigation (Agutter 2008). Since no detailed explanatory mechanism for this evolutionary conserved phenomenon currently exists, unification of the hormesis-nomenclature is thwarted.…”

“…"Adaptive" relates to intrinsic self-recovery mechanisms up-regulated in response to exposure to stress and possibly over-activation of these processes as a means of coping with the unpredictability of exposure to subsequent (other) stresses. The biphasic dose-response pattern is now generally thought to reflect the activation of the adaptive capacity of biological systems in response to stress (Agutter 2008;Mattson 2008).…”

“…The phenomenon of postconditioning hormesis is not yet widely accepted. In this respect, Agutter (2008) recently questioned the generality of this phenomenon: whether it was indeed observed in numerous different biological systems or whether its occurrence is more restricted. Moreover, it was questioned whether this phenomenon has been observed at the cellular level or only in the context of multicellular organisms such as humans.…”

Hormesis and Cellular Quality Control: A Possible Explanation for the Molecular Mechanisms that Underlie the Benefits of Mild Stress

“…It has for long been proposed that hormesis, the brief exposure to periods of mild stress, which are damaging or detrimental at higher doses, can trigger an adaptive and beneficial effect by enhancing the cells resistance to similar or more severe stress Baldwin 1997, 2001;Stebbing 2003aStebbing , 2003bAgutter 2008).…”