An Overview of the Circadian Clock in the Frame of Chronotherapy: From Bench to Bedside

Abstract

Most living organisms in both the plant and animal kingdoms have evolved processes to stay in tune with the alternation of day and night, and to optimize their physiology as a function of light supply. In mammals, a circadian clock relying on feedback loops between key transcription factors will thus control the temporally regulated pattern of expression of most genes. Modern ways of life have highly altered the synchronization of human activities with their circadian clocks. This review discusses the links between an altered circadian clock and the rise of pathologies. We then sum up the proofs of concept advocating for the integration of circadian clock considerations in chronotherapy for health care, medicine, and pharmacotherapy. Finally, we discuss the current challenges that circadian biology must face and the tools to address them.

Evaluating the Relationship between Circadian Rhythms and Sleep, Metabolic and Cardiovascular Disorders: Current Clinical Evidence in Human Studies

“…Broader than the concept of sleep hygiene, circadian hygiene-based interventions and programs would have to take into account necessary changes in every aspect of social life [ 81 , 82 ]. Understanding the underlying mechanisms that regulate circadian rhythm may provide insights into circadian physiology and advance novel chronotherapy approaches and therapeutic targets for metabolic disorders [ 83 , 84 , 85 ].…”

Circadian Rhythm Sleep-Wake Disorders

“…An estimated 40% of protein-coding genes display 24-hour rhythmicity in mammals, which suggests that a considerable portion of the transcriptome is controlled by the circadian system 3 …”

“…A high-fat diet can disrupt synchrony between central and peripheral clocks. Food intake in the circadian evening or night is associated with a greater amount of body fat, obesity, and decreased effectiveness of weight loss treatments for adults and children 3 . Intestinal microbiota depletion can disrupt peripheral clocks, with subsequent alterations in corticosteroid levels that can contribute to metabolic disorders 6 …”

“…Epigenetic and posttranscriptional regulation also contribute to the molecular clockwork. These regulatory mechanisms affect genes that encode products involved in cellular physiology and metabolism: enzymes, portions of the ubiquitin-proteosome pathway, transporters from the nucleus to the cytoplasm, noncoding RNAs, and remodelers of chromatin 3 . In addition, diet (specifically one that is high in fat) and timing of dietary intake can reprogram the circadian rhythmicity of regions in the brain (eg, the suprachiasmatic nucleus) and of peripheral clocks.…”

“…A delayed chronotype correlates with an increased prevalence of psychological disorders, diabetes, poorer cardiovascular health, and a higher risk of mortality. Chronotype changes with age; older people tend to have dampened oscillations in several circadian traits, such as the release of melatonin and cortisol hormones, which could be linked to some age-related pathologies 3 …”