Circadian rhythm

Circadian rhythm
Name	Circadian rhythm
Field	Chronobiology
Discovered	18th century
Keywords	sleep–wake cycle, suprachiasmatic nucleus, melatonin

Circadian rhythm Circadian rhythm are endogenous, approximately 24-hour biological oscillations that organize physiology and behavior in many organisms. They coordinate processes across scales from molecular gene expression to organismal sleep–wake patterns, aligning internal timekeeping with external cycles such as the solar day and seasonal changes. Research spans contributions from Jean-Jacques d'Ortous de Mairan, Franz Halberg, Colin Pittendrigh, and institutions like the Salk Institute and Max Planck Society.

Overview and definition

The term denotes daily rhythmicity observed in organisms including Homo sapiens, Drosophila melanogaster, Mus musculus, Neurospora crassa, and Arabidopsis thaliana that persists under constant conditions. Descriptions draw on classic experiments by Jean-Jacques d'Ortous de Mairan and formalization by Franz Halberg and Colin Pittendrigh, while modern frameworks integrate work at the National Institutes of Health and Howard Hughes Medical Institute. Key measurable outputs include locomotor activity, hormone secretion, body temperature, and gene expression quantified in laboratories such as the Salk Institute for Biological Studies and the Max Planck Institute for Biophysical Chemistry.

Biological mechanisms

Central timekeeping in vertebrates resides in the suprachiasmatic nucleus located in the hypothalamus near the optic chiasm, receiving retinal input via the retinohypothalamic tract studied by researchers at Harvard Medical School and University of Cambridge. Peripheral oscillators exist in tissues like the liver, heart, and adrenal glands; notable work on liver clocks was performed at University of California, San Diego and University of Oxford. Neurochemical mediators include melatonin produced by the pineal gland, norepinephrine from the locus coeruleus, and neurotransmission involving glutamate at retinal projections noted in studies from Johns Hopkins University and Karolinska Institutet.

Genetics and molecular clock

Key clock genes were identified in genetic screens in Drosophila melanogaster (e.g., period, timeless, clock) and in mammals (Per1, Per2, Cry1, Cry2, Bmal1) through work at Brandeis University, Massachusetts Institute of Technology, University of Geneva, and Stanford University. Transcriptional-translational feedback loops described by Michael Rosbash, Jeffrey C. Hall, and Michael W. Young underpin oscillations; these researchers received recognition from the Nobel Prize in Physiology or Medicine. Post-translational modifications involve kinases such as CK1epsilon/CK1delta explored at Yale University and phosphatases characterized at University of California, San Francisco.

Physiological and behavioral functions

Circadian organization regulates sleep architecture studied in sleep clinics at Mayo Clinic and Cleveland Clinic, metabolism research at Imperial College London, cardiovascular timing investigated at Mount Sinai Hospital, and immune rhythms researched at University College London and Johns Hopkins Bloomberg School of Public Health. Behavioral outputs include feeding rhythms seen in Rattus norvegicus and seasonal breeding in species studied at Smithsonian Institution collections. Clinical implications connect to chronotherapy trials at Memorial Sloan Kettering Cancer Center and shift-work epidemiology analyzed by researchers at World Health Organization and International Agency for Research on Cancer.

Entrainment and environmental cues

Light is the principal zeitgeber transduced by intrinsically photosensitive retinal ganglion cells containing melanopsin, a discovery advanced at University of Toronto and Scripps Research. Nonphotic cues include feeding schedules investigated at Rockefeller University and temperature cycles characterized in studies from Princeton University. Social zeitgebers were emphasized by investigators at University of Pittsburgh and the National Institute of Mental Health. Jet lag and shift work have been modeled in experiments at NASA and European Space Agency facilities.

Disorders and clinical relevance

Disorders include delayed and advanced sleep phase syndromes with genetic links identified in cohorts at University of Copenhagen and Karolinska Institutet, non-24-hour sleep–wake disorder prevalent in blind individuals studied at University of California, Los Angeles, and circadian disruption implicated in metabolic syndrome research at Johns Hopkins University School of Medicine. Chronobiological aspects of mood disorders were explored at McLean Hospital and University of Oxford, while cancer timing and survival correlations were reported from studies at Dana–Farber Cancer Institute and MD Anderson Cancer Center.

Research methods and experimental models

Approaches include genetic model systems (Drosophila melanogaster, Mus musculus, Neurospora crassa, Arabidopsis thaliana), in vitro reporter assays developed at Cold Spring Harbor Laboratory, and in vivo imaging techniques advanced at Max Planck Institute for Medical Research and California Institute of Technology. Chronobiology employs actigraphy used in clinical centers like Stanford Health Care, polysomnography standardized by American Academy of Sleep Medicine, and transcriptomics pipelines established at Broad Institute. Field studies utilize longitudinal cohorts supported by institutions such as the Framingham Heart Study and datasets curated by National Institutes of Health.

Category:Chronobiology