Impacts of Microgravity on Circadian Rhythms and Regulatory Mechanisms

The circadian clock is an endogenous mechanism governing physiological and behavioral processes, with a period of ~24 h to adapt to the cycling environmental cues, e.g., light and temperature. Desynchronization of the circadian rhythm results in compromised adaptability and viability. In mammals, including humans, circadian misalignment causes a variety of physiological and health challenges, such as sleep disorders, disturbance in metabolic homeostasis, decreased immunity, affectional diseases, increased risk of tumorigenesis, and even a shortened life span. The space environment dramatically differs from that on the surface of Earth, and space environmental cues, including microgravity, special lighting conditions, magnetic field, and radiation, have differential impacts on the circadian rhythm. Among these factors, the force of gravity has remained constantly present over the course of development and evolution for all lives on Earth, while it is absent or different in space. Since the middle of the last century, it has been demonstrated that microgravity can elicit extensive changes in circadian rhythms; however, systematic exploration is still needed for comprehensive understanding. In this review, we summarize analogs for simulating microgravity, the basic knowledge of the molecular regulation of circadian clocks in various model organisms, findings about the effects of microgravity on circadian rhythms, and the underlying mechanisms, which remain largely unclear by far. We also raise some prospects on these issues and research on which would benefit the improvement of health and performance of orbital astronauts and future extraterrestrial habitation.