Human Circadian Timing System and Sleep-Wake Regulation

The circadian pacemaker (or biologic clock) confers endogenous rhythmicity with a period just slightly greater than 24 hours, persists in the absence of periodic changes in the external environment, and has timing or phase relative to the time of day that is genetically determined and influenced by environmental synchronizers. Under appropriate conditions, melatonin, body temperature, and many other physiologic processes can be used to assess circadian phase or biologic clock time. Although environmental light-dark schedules are the primary circadian synchronizer, other nonphotic stimuli such as exercise can shift circadian phase. The circadian pacemaker interacts with sleep-wake regulatory processes to influence many physiologic variables: hormone levels, autonomic nervous system activity, neurobehavioral performance, and the propensity for and timing and internal structure of sleep. Environmental, social, behavioral, and genetic factors, pharmacologic agents, and age influence most elements of this system. This chapter emphasizes, for the benefit of the student and the practitioner, the complexity of interactions of the circadian pacemaker and the sleep homeostat in regulating physiology, with important implications for health, performance, and clinical practice.