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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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The redox rhythm gates immune-induced cell death distinctly from the genetic clock
Organisms use circadian clocks to synchronize physiological processes to anticipate the Earth’s day-night cycles and regulate responses to environmental signals to gain competitive advantage. While divergent genetic clocks have been studied extensively in bacteria, fungi, plants, and animals, an ancient conserved circadian redox rhythm has been recently reported. However, its biological function and physiological outputs remain elusive. Here, we uncovered the coexistence of redox and genetic rhythms with distinct period lengths and transcriptional targets through concurrent metabolic and transcriptional time-course measurements in anArabidopsislong-period clock mutant. Analysis of the target genes indicated regulation of the immune-induced programmed cell death (PCD) by the redox rhythm. Moreover, this time-of-day-sensitive PCD was eliminated by redox perturbations and by blocking the signaling pathway of the plant defense hormones jasmonic acid/ethylene, while remaining intact in genetic clock-defective backgrounds. This study shows that compared to robust genetic clocks, the more sensitive circadian redox rhythm serves as a signaling hub in regulating incidental energy-intensive processes, such as immune-induced PCD involving reprogramming of chloroplast and mitochondria activities, to provide organisms a flexible strategy to mitigate metabolic overload during stress responses.
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- Award ID(s):
- 2109302
- PAR ID:
- 10635429
- Publisher / Repository:
- Proceedings of the National Academy of Sciences
- Date Published:
- Journal Name:
- Proceedings of the National Academy of Sciences
- Volume:
- 122
- Issue:
- 37
- ISSN:
- 0027-8424
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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