Our bodies are subject to regular and predictable fluctuations in environmental conditions, to which they adapt through changes in alertness, and metabolic, cardiovascular, immune and other functions. This does not result from a passive, acute response to these external changes, but rather the activity of an endogenous timekeeping mechanism operating on an approximately daily basis. This mechanism is called the circadian clock and is present in most cells of our body. To orchestrate all daily changes in their complexity in alignment with environmental changes, clocks are organized hierarchically in a system with a central clock in the suprachiasmatic nuclei of the hypothalamus (SCN) that directly senses them, entrains accordingly, and controls output rhythms in physiological variables that can synchronize clocks in other parts of the body. Internal synchrony is a prerequisite for proper function of the entire system. In humans, the disruption of synchrony (chronodisruption) is associated with unhealthy lifestyle habits prevalent in modern societies, leading to “civilization diseases” such as sleep, mood, and cardio-metabolic disorders. To mitigate the consequences of circadian disruption, we need to gain more insight into the circadian regulation of physiological processes by employing time-resolved analyzes at the cellular, organ/tissue, system, and population levels. In this lecture, we will demonstrate how the central clock achieves multilevel synchrony among clocks in other parts of the brain and in selected peripheral tissues. In the results from animal studies, we will focus on the role of glucocorticoids and feeding as two prominent signals controlled by the SCN clock, using in vivo and in vitro techniques, including real-time monitoring of circadian clocks in organotypic explants and circadian transcriptomics. Finally, we will present our recent data from a human population-representative study in which we uncovered a link between circadian misalignment and biomarkers of cardiovascular and metabolic diseases.
Prof. PharmDr. Alena Sumová, CSc., DSc. has been the head of the Laboratory of Biological Rhythms at the Institute of Physiology (IPHYS) of the Czech Academy of Sciences since 1999. She has been working in the field of circadian rhythms for more than 30 years and has published 110 papers in this research area (H-index 31).