Living beings have an internal clock that regulates biological functions in a 24-hour period. This is also known as circadian rhythm and allows for adaptation to cyclic changes in the environment.
The conductor, or master clock, is located in the brain, called the hypothalamus in human beings, or more specifically the suprachiasmatic nucleus. This is where thousands of neurons carry out activities that oscillate over a period of close to 24 hours dictated by about fifteen genes called “clock genes”[1].
This cyclic activity extends to the various organs which are synchronised by the hypothalamus but also adapt to their local environment. A primate study found that the majority of coding genes have cyclic expression within 24 hours in most organs. Remarkably, less than 1% of genes whose expression is rhythmic in a tissue revealed cyclic expression in other tissues, this demonstrates the importance and specificity of peripheral clocks in organs[2].
These biological clocks are also sensitive to different signals that act as synchronizers, for example, light is key to synchronize the master clock in the brain. Special photoreceptors in the retina – melanopsin-expressing ganglion cells – transmit a signal to the suprachiasmatic nucleus and synchronize the clock at a rate of 24 hours[3]. Light intensity, duration of exposure and spectral range are key parameters in this phenomenon[4]. Other factors also influence peripheral clocks including diet, especially at the liver level[5], and physical exercise in muscle tissue[6].
These mechanisms of regulation play a central role in affective, cognitive, and metabolic functions and their dysfunction can lead to severe health problem: increased risk of sleep disorders, metabolic and cardiovascular disorders, cancers[7], impaired cognitive function, depression and anxiety. Multiple other factors are also involved, including genetic background, lifestyle and behaviors (light hygiene, diet, night work, stress), certain diseases or special sensitivity to light and other synchronizers.
[1] Chronobiologie, https://www.inserm.fr/information-en-sante/dossiers-information/chronobiologie
[2] D Mure LS et al., Diurnal transcriptome atlas of a primate across major neural and peripheral tissues. Science. 2018 Mar 16;359(6381)
[3] Hattar S et al., Central projections of melanopsin-expressing retinal ganglion cells in the mouse.J Comp Neurol. 2006 Jul 20;497(3):326-49.
[4] Gronfier C., Circadian clock and non-visual functions: the role of light in humans. Biol Aujourdhui. 2014;208(4):261-7
[5] Tognini P et al., Distinct Circadian Signatures in Liver and Gut Clocks Revealed by Ketogenic Diet. Cell Metab. 2017 Sep 5;26(3):523-538.e5.
[6] Elizabeth A. Schroder and Karyn A. Esser, Circadian Rhythms, skeletal muscle molecular clocks and exercise, Exercise and Sport Sciences Reviews. 41(4):224–229, OCT 2013
[7] Loning Fu and Nicole M. Kettner, The Circadian Clock in Cancer Development and Therapy, Prog Mol Biol Transl Sci. 2013; 119: 221–282.
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