Allostatic breakdown of cascading homeostat systems: A computational approach.

Homeostasis posits that physiological systems compensate setpoint deviations in an attempt to maintain a state of internal constancy. Allostasis, on the other hand, suggests that physiological regulation is more appropriately described by predictive modulatory actions that, by adjusting setpoints, anticipate and react to changes in internal and external demand. In other words, "maintaining stability through change." The allostatic perspective enabled the rationalization of predictive and reactive homeostasis. While the latter reflects external perturbations, the former refers to systemic adaptation in response to anticipated changes - not necessarily related to unexpected external disturbances. Therefore, the concept of allostasis accounts also for adaptation to circadian variations (seasonal, circannual or other predictive variability) and interprets the system's adaptation of its setpoints not as reactive/subnormal adjustments, but rather as a proper response. Therefore, systemic entrainment to periodic demands is handled by predicting and implementing setpoint changes. Given the important role of circadian variability and regulation in maintaining health, and the loss of circadian entrainment as a predisposing factor and sequel of stress, we elaborate on an allostasis model which demonstrates the ability of the systems to adapt to circadian demands and quantifies the deteriorative natural wear and tear of a system constantly adapting, i.e. the irreversible damage and its consequences on system function and overall survival. While developing a system of cascaded nature, we demonstrate the importance of phase coordination and the implications of maintaining proper phase relations. The disruption of these relations is a hallmark of circadian disruption, a predisposing factor to increased vulnerability and/or a sequel to chronic stress.