Neurobiology and genetics of circadian rhythms

Abstract

There have been remarkable advances in our understanding of the molecular, cellular and physiological mechanisms underlying the regulation of circadian rhythms, as well as the impact of circadian dysfunction on health and disease. The concept of circadian health captures the necessity of proper function of internal body clocks and their synchronization with external influences such as the light/dark cycle, lifestyle choice and work/school schedules. The discovery of the molecular mechanisms generating circadian rhythms received the Nobel Prize in Physiology or Medicine in 2017. This discover, coupled with the recent findings that circadian clocks are found in nearly all cells and tissues, and that nearly 40% of entire genome is rhythmic have broadened our view of the impact of circadian rhythms on health. In addition to timing, circadian clocks regulate cellular bioenergetics, inflammation and cell division. It is now evident that circadian dysfunction can play a role in a wide range of pathology, from the increased risk for cardio-metabolic disease and malignancy in shift workers, to the changes in circadian amplitude that often precede the clinical symptoms of neurodegenerative disorders, such as Alzheimer’s Disease and Parkinson Disease. The rhythmic expression of genes, proteins and metabolites in humans, offer new opportunities to examine circadian timing by using computational quantification of temporal organization as diagnostic biomarkers in the clinic.