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Dynamics of a Multistage Circadian System

Tissues throughout the body exhibit circadian rhythms, forming a multioscillatory system whose disruption results in jet lag and other health problems in travelers and rotational shift workers. The authors’ simulations of the dynamics of a multistage circadian system (based on experimental results for nocturnal rodents) reveal the flexibility and stability inherent in a multistage system, as well as potential pitfalls. The modeling predicts that jet lag tends to be most severe following an eastward change of 5 to 8 time zones due to prolonged desynchrony of the system. This desynchrony is partly due to differing reentrainment rates among components, but a much greater source of desynchrony is the antidromic reentrainment of some but not all components (reentrainment by partition), triggered by the overshoot of the master pacemaker’s phase in response to these advances. Based on the multistage system dynamics, the authors design a simple protocol that results in a more orderly transition that avoids antidromic reentrainment in all components, thereby reducing the reentrainment time from nearly 2 weeks to just a few days for the most difficult shifts. The authors compare the predicted behavior of self-sustaining versus damped oscillatory components in the system as well as the effect of weak versus strong coupling from the master pacemaker to the peripheral components.