Abstract
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.
Highlights
Adapting to the environment across different geophysical locations is a spontaneous tendency of life on the Earth prompted by progressive evolution
Interlocking feedback loops provide robustness against noise and environmental perturbations to maintain accuracy in circadian timing. The existence of these cooperatives helps to generate phase delays in circadian transcriptional output, which temporally regulates the expression of clock-controlled output genes and other circadian rhythm-related genes for tuning internal physiology [2]
The circadian system is hierarchically organized with the suprachiasmatic nucleus (SCN) network-based master pacemaker in the central nervous systems
Summary
Adapting to the environment across different geophysical locations is a spontaneous tendency of life on the Earth prompted by progressive evolution. Axial rotation of Earth causes day/night cycles around 24-h This brings periodic fluctuations in light exposure, light intensity, and environmental temperature every day. It influences all organisms immensely in terms of many aspects of their physiology and behavior. To adopt such periodical changes, most organisms have been equipped with internal biological clocks that antedates day and night cycles. Recent studies have suggested that circadian systems in mammals consist of several internal clocks across the entire body [1]. These clocks, located in different tissues, are. In future, such deep understanding would certainly help us in reimagining the potential scopes of chronotherapeutic interventions
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