The physiological significance of the circadian dynamics of the HPA axis: Interplay between circadian rhythms, allostasis and stress resilience

Abstract

Circadian time-keeping mechanisms preserve homeostasis by synchronizing internal physiology with predictable variations in the environment and temporally organize the activation of physiological signaling mechanisms to promote survival and optimize the allocation of energetic resources. In this paper, we highlight the importance of the robust circadian dynamics of allostatic mediators, with a focus on the hypothalamic-pituitary-adrenal (HPA) axis, for the optimal regulation of host physiology and in enabling organisms to adequately respond and adapt to physiological stressors. We review studies showing how the chronic disruption of circadian rhythms can result in the accumulation of allostatic load, which impacts the appropriate functioning of physiological systems and diminishes the resilience of internal systems to adequately respond to subsequent stressors. A careful consideration of circadian rhythm dynamics leads to a more comprehensive characterization of individual variability in allostatic load and stress resilience. Finally, we suggest that the restoration of circadian rhythms after pathological disruption can enable the re-engagement of allostatic mechanisms and re-establish stress resilience.

Keywords: Allostasis; Chronopharmacology; Circadian rhythms; Glucocorticoids; HPA axis; Mathematical modeling; Stress resilience.