Intrinsic near-24-h pacemaker period determines limits of circadian entrainment to a weak synchronizer in humans

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Abstract
Endogenous circadian clocks are robust regulators of physiology and behavior. Synchronization or entrainment of biological clocks to environmental time is adaptive and important for physiological homeostasis and for the proper timing of species-specific behaviors. We studied subjects in the laboratory for up to 55 days each to determine the ability to entrain the human clock to a weak circadian synchronizing stimulus [scheduled activity–rest cycle in very dim (≈1.5 lux in the angle of gaze) light–dark cycle] at three ≈24-h periods: 23.5, 24.0, and 24.6 h. These studies allowed us to test two competing hypotheses as to whether the period of the human circadian pacemaker is near to or much longer than 24 h. We report here that imposition of a sleep–wake schedule with exposure to the equivalent of candlelight during wakefulness and darkness during sleep is usually sufficient to maintain circadian entrainment to the 24-h day but not to a 23.5- or 24.6-h day. Our results demonstrate functionally that, in normally entrained sighted adults, the average intrinsic circadian period of the human biological clock is very close to 24 h. Either exposure to very dim light and/or the scheduled sleep–wake cycle itself can entrain this near-24-h intrinsic period of the human circadian pacemaker to the 24-h day.