The award of the Nobel Prize in Physiology 2017 to Hall, Rosbash, and Young for their groundbreaking discoveries into mechanisms regulating circadian rhythms has contributed to greater scientific appreciation and recognition for the field of circadian physiology. The origins of circadian physiology certainly date back multiple decades and even centuries. First demonstrations of controlled endogenous circadian rhythms in plants by Mairan and Candolle in the 18th century paved the way for more recent groundbreaking discoveries into regulation of mammalian circadian function made by pioneering 20th-century physiologists Pittendrigh and Aschoff (10). In the 21st century, research into circadain physiology has been fueled by discoveries into the genetic mechanisms of the circadian rhythm generation deemed essential for organismal adaption to the 24-h environmental cycles in nearly all living organisms (14). More recently, circadian research has been further fueled by circadian etiology of common chronic diseases such as diabetes, cancer, heart disease, and neurodegeneration.

In mammals, the circadian system is organized as a multi-level hierarchical oscillator network. The “central clock” of the circadian system in mammals is localized in the suprachiasmatic nucleus (SCN) of the hypothalamus, where it functions to synchronize cell-autonomous circadian oscillators present in a wide array of peripheral tissues via a combination of neuronal, humoral, and behavioral cues. The composition of the molecular clock in the SCN and peripheral tissues consists of transcriptional activators CLOCK and its heterodimer BMAL1, and repressor genes that encode period (PER1, 2) and cryptochrome (CRY1, 2) proteins, in addition to secondary regulatory loops that provide molecular stabilization by acting as respective repressors and activators of Bmal1 (14). The CLOCK: BMAL1 heterodimer is essential for the generation of circadian rhythms of transcription through DNA binding to conserved promoter regions along with concurrent recruitment of cell-specific enhancers and repressors for regulation of cell-specific target genes (14). Importantly, this complex regulatory mechanism ensures the generation of robust 24-h cycles of transcription and translation with varying phases of expression, which are optimal for cell-specific functionality, proliferation, and survival. Thus numerous essential cellular physiological functions (eg, mitochondrial function, ion channel activation, inflammatory responses, substrate metabolism, and many more) display robust circadian rhythmicity due to transcriptional control by the circadian clock.