Multi-Modal Regulation of Circadian Physiology by Interactive Features of Biological Clocks

SIMPLE SUMMARY: Circadian rhythms, driven by molecular clockwork, exist in nearly all cells and tissues throughout the body, and these rhythmic oscillators constitute tightly coupled network systems that generate rhythmic physiology and behavior. Common circadian disrupting factors, such as night shift work and mistimed eating, can increase the risk of disease onset and symptoms. Disease can then, in turn, promote circadian disruption, leading to a vicious cycle of adverse circadian and overall health effects. This relationship suggests the importance of well-coordinated internal clock systems that maintain optimal synchrony with environmental and metabolic cues. In this review, we will recount the recent advances in circadian clock research and discuss how circadian clocks reciprocally interact with other signaling and metabolic factors to coordinate the daily rhythms of physiology. ABSTRACT: The circadian clock is a fundamental biological timing mechanism that generates nearly 24 h rhythms of physiology and behaviors, including sleep/wake cycles, hormone secretion, and metabolism. Evolutionarily, the endogenous clock is thought to confer living organisms, including humans, with survival benefits by adapting internal rhythms to the day and night cycles of the local environment. Mirroring the evolutionary fitness bestowed by the circadian clock, daily mismatches between the internal body clock and environmental cycles, such as irregular work (e.g., night shift work) and life schedules (e.g., jet lag, mistimed eating), have been recognized to increase the risk of cardiac, metabolic, and neurological diseases. Moreover, increasing numbers of studies with cellular and animal models have detected the presence of functional circadian oscillators at multiple levels, ranging from individual neurons and fibroblasts to brain and peripheral organs. These oscillators are tightly coupled to timely modulate cellular and bodily responses to physiological and metabolic cues. In this review, we will discuss the roles of central and peripheral clocks in physiology and diseases, highlighting the dynamic regulatory interactions between circadian timing systems and multiple metabolic factors.