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Understanding Quantitative Circadian Regulations Are Crucial Towards Advancing Chronotherapy

by 1,2,†, 1,2,†, 1,2,* and 1,2,*
1
HKBU Institute for Research and Continuing Education, Shenzhen 518057, China
2
Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong 999077, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Cells 2019, 8(8), 883; https://doi.org/10.3390/cells8080883
Received: 10 May 2019 / Revised: 1 August 2019 / Accepted: 9 August 2019 / Published: 13 August 2019
Circadian rhythms have a deep impact on most aspects of physiology. In most organisms, especially mammals, the biological rhythms are maintained by the indigenous circadian clockwork around geophysical time (~24-h). These rhythms originate inside cells. Several core components are interconnected through transcriptional/translational feedback loops to generate molecular oscillations. They are tightly controlled over time. Also, they exert temporal controls over many fundamental physiological activities. This helps in coordinating the body’s internal time with the external environments. The mammalian circadian clockwork is composed of a hierarchy of oscillators, which play roles at molecular, cellular, and higher levels. The master oscillation has been found to be developed at the hypothalamic suprachiasmatic nucleus in the brain. It acts as the core pacemaker and drives the transmission of the oscillation signals. These signals are distributed across different peripheral tissues through humoral and neural connections. The synchronization among the master oscillator and tissue-specific oscillators offer overall temporal stability to mammals. Recent technological advancements help us to study the circadian rhythms at dynamic scale and systems level. Here, we outline the current understanding of circadian clockwork in terms of molecular mechanisms and interdisciplinary concepts. We have also focused on the importance of the integrative approach to decode several crucial intricacies. This review indicates the emergence of such a comprehensive approach. It will essentially accelerate the circadian research with more innovative strategies, such as developing evidence-based chronotherapeutics to restore de-synchronized circadian rhythms. View Full-Text
Keywords: circadian rhythms; transcriptional dynamics; molecular clockwork; chronotherapy circadian rhythms; transcriptional dynamics; molecular clockwork; chronotherapy
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Chowdhury, D.; Wang, C.; Lu, A.-P.; Zhu, H.-L. Understanding Quantitative Circadian Regulations Are Crucial Towards Advancing Chronotherapy. Cells 2019, 8, 883.

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