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The circadian clock in mammals regulates the sleep/wake cycle and many associated behavioral and physiological processes. The cellular clock mechanism involves a transcriptional negative feedback loop that gives rise to circadian rhythms in gene expression with an approximately 24-hour periodicity. To maintain system robustness, clocks throughout the body must be synchronized and their functions coordinated. In mammals, the master clock is located in the suprachiasmatic nucleus (SCN) of the hypothalamus. The SCN is entrained to the light/dark cycle through photic signal transduction and subsequent induction of core clock gene expression. The SCN in turn relays the time-of-day information to clocks in peripheral tissues. While the SCN is highly responsive to photic cues, peripheral clocks are more sensitive to non-photic resetting cues such as nutrients, body temperature, and neuroendocrine hormones. For example, feeding/fasting and physical activity can entrain peripheral clocks through signaling pathways and subsequent regulation of core clock genes and proteins. As such, timing of food intake and physical activity matters. In an ideal world, the sleep/wake and feeding/fasting cycles are synchronized to the light/dark cycle. However, asynchronous environmental cues, such as those experienced by shift workers and frequent travelers, often lead to misalignment between the master and peripheral clocks. Emerging evidence suggests that the resulting circadian disruption is associated with various diseases and chronic conditions that further circadian desynchrony and accelerate disease progression. In this review, we discuss how sleep, nutrition, and physical activity synchronize circadian clocks and how chronomedicine may offer novel strategies for disease intervention.
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Modeling the Effects of Napping and Non-napping Patterns of Light Exposure on the Human Circadian Oscillator
In early childhood, consolidation of sleep from a biphasic to a monophasic sleep-wake pattern, that is, the transition from sleeping during an afternoon nap and at night to sleeping only during the night, represents a major developmental milestone. Reduced napping behavior is associated with an advance in the timing of the circadian system; however, it is unknown if this advance represents a standard response of the circadian clock to altered patterns of light exposure or if it additionally reflects features of the developing circadian system. Using a mathematical model of the human circadian pacemaker, we investigated the impact of napping and non-napping patterns of light exposure on entrained circadian phases. Simulated light schedules were based on published data from 20 children (34.2 ± 2.0 months) with habitual napping or non-napping sleep patterns (15 nappers). We found the model predicted different circadian phases for napping and non-napping light patterns: both the decrease in afternoon light during the nap and the increase in evening light associated with napping toddlers’ later bedtimes contributed to the observed circadian phase difference produced between napping and non-napping light schedules. We systematically quantified the effects on phase shifting of nap duration, timing, and light intensity, finding larger phase delays occurred for longer and earlier naps. In addition, we simulated phase response curves to a 1-h light pulse and 1-h dark pulse to predict phase and intensity dependence of these changes in light exposure. We found the light pulse produced larger shifts compared with the dark pulse, and we analyzed the model dynamics to identify the features contributing to this asymmetry. These findings suggest that napping status affects circadian timing due to altered patterns of light exposure, with the dynamics of the circadian clock and light processing mediating the effects of the dark pulse associated with a daytime nap.
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- Award ID(s):
- 1853511
- PAR ID:
- 10430566
- Publisher / Repository:
- SAGE Publications
- Date Published:
- Journal Name:
- Journal of Biological Rhythms
- Volume:
- 38
- Issue:
- 5
- ISSN:
- 0748-7304
- Format(s):
- Medium: X Size: p. 492-509
- Size(s):
- p. 492-509
- Sponsoring Org:
- National Science Foundation
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