Counteracting health risks by Modulating Homeostatic Signaling.

Homeostasis was initially conceptualized by Bernard and Cannon around a century ago as a steady state of physiological parameters that vary within a certain range, such as blood pH, body temperature, and heart rate [1,2]. The underlying mechanisms that maintain homeostasis are explained by negative feedbacks that are executed by the neuronal, endocrine, and immune systems. At the cellular level, homeostasis, such as that of redox and energy steady state, also exists and is regulated by various cell signaling pathways. The induction of homeostatic mechanism is critical for human to adapt to various disruptive insults (stressors); while on the other hand, adaptation occurs at the expense of other physiological processes and thus runs the risk of collateral damages, particularly under conditions of chronic stress. Conceivably, anti-stress protection can be achieved by stressor-mimicking medicinals that elicit adaptive responses prior to an insult and thereby serve as health risk countermeasures; and in situations where maladaptation may occur, downregulating medicinals could be used to suppress the responses and prevent subsequent pathogenesis. Both strategies are preemptive interventions particularly suited for individuals who carry certain lifestyle, environmental, or genetic risk factors. In this article, we will define and characterize a new modality of prophylactic intervention that forestalls diseases via modulating homeostatic signaling. Moreover, we will provide evidence from the literature that support this concept and distinguish it from other homeostasis-related interventions such as adaptogen, hormesis, and xenohormesis. [Display omitted] • Various theories exist on how to enhance the balance of biological systems with medicinal and behavioral interventions. • Modulant of Homeostatic Signaling (MHS) denotes interventions that act as "tuners" of specific adaptive responses via relevant signaling targets. • "Tune-up" MHS (TUMHS) acts as a stress mimic that elicits protective adaptive responses, hence preventing damages caused by an upcoming stress. • "Tune-down" MHS (TDMHS) acts as a damper of chronic, detrimental adaptive responses that predispose individuals to a variety of chronic diseases. • Both TUMHS and TDMHS are particularly suitable as risk countermeasures for individuals who carry lifestyle, environmental, and genetic risks, such as the risks for mismatch diseases. [ABSTRACT FROM AUTHOR]