Circadian clock, sleep and the regulation of the human body

27.09.2016  /  Scienceandmore  /  Category: Human Biology

The circadian rhythm, also called circadian clock or just inner clock, is the endogenous capability of an organism to retain a 24 h rhythm without being exposed to environmental stimuli that indicate the time of day. Animals, plants and even fungi generate a circadian rhythm and plays a major role in daily live.

For humans it is the mechanism to regulate sleep and wakefulness. Interestingly, during the first half year of life, as infants, humans do not have a working circadian rhythm, which explains why babies have an erratic sleeping pattern. They wake up in the middle of the night and are wide awake, much to the suffering of the parents. At around three to six months of age, the circadian clock starts to get established, and babies begin to sleep at night and are awake during the day.

How are sleep and wakefulness regulated?

There are two mechanisms or systems that take care of sleep and wakefulness. This first is the “sleep and wake homoeostasis”, which is a balance-system of sleep and wakefulness. It measures the ratio of both, and in case of insufficient sleep over a longer period of time the need for sleep will accumulate, resulting in the enhanced feeling of sleepiness. The sleep-wake homoeostasis system is also responsible for continuous sleep throughout the night.

The second regulator of sleep and wakefulness is the circadian clock, and it regulates the timing of both states. In general, the circadian clock’s strongest effect on sleep occurs between 2 and 4 o’clock at night, when people are in their deepest sleep. At this time, the body’s production of the sleep hormone melatonin is at its highest level.

Upon awakening in the morning, melatonin levels are strongly reduced, and instead stress hormone levels, such as cortisol, rise. This is also the time when the circadian clock ensures that the body’s digestive system is animated and that the brain starts to reach peak performance; ready for analysing, decision making, altogether ready for work.

In the afternoon, the circadian clock improves motor-control to ensure peak physically performance.

In the evening, the circadian clock prepares the organism for sleep by slowing down the metabolism, reducing stress-hormone levels and again increasing melatonin levels that reach peak levels between 2 and 4 o’clock at night; thereby closing the cycle.

Overall, the circadian clock gets the organism into a rhythm that attunes it for reoccurring events and regulates daily processes. But how is rhythm regulated?

Light and darkness are the key players here, especially the timing when they are perceived. Light, obviously, is sensed by specific photoreceptors of the eye’s retina. Studies in rodents found that entrainment of the circadian rhythm depends on melanopsin that has peak sensitivity to light of around 480 nm wavelength, and opsin of the cones that has peak sensitivity to light of above 500 nm wavelength (middle wavelength-opsin in the outer retina). Therefore, melanopsin perceive the blue light proportion of daylight and conveys blue light signals. The participation of other retina photopigments in entrainment is, however, not excluded.

Light scale with wavelength

The subsequently created signal is transferred to an area in the brains that is part of the hypothalamus and is called Suprachiasmatic Nucleus (SCN), or “master clock”. During the day, melanopsin-mediated stimulation of the SCN prevents the production of the sleep hormone melatonin, resulting in wakefulness. Conversely, during the evening/night, when blue light mediated stimulation of the SCN is reduced, melanin is produced, resulting in sleepiness. The SCN is also responsible for the downregulation of the core body temperature at this time. Thus, the feeling of being cold is much stronger during the night.

The inhibiting effect of blue light on the melatonin production at night could results in low-quality sleep during the night. This is where people’s most common hobby, work and general pursuit come into play: computers, tablets, phones and their screens. They emit blue light and we use them until late at night; we have a quick look at our phones before we go to sleep. By doing so, the circadian clock gets jumbled and, thereby, the whole day-night rhythm. This could results in difficulties to fall asleep, light sleep and a feeling of being unrested.
Circadian Rhythm Human 2

Helpful tips for better sleep

Interruptions of sleep at night should be avoided, and in case that this is not possible, for instance by a visit of the bathroom, light should not be switched on. Of course only in case it is ensured that movement in the house, flat, rooms, and so on, during darkness is safe!

It is important to realise that closed eyes do not prevent light from being perceived and the resulting signal from being transferred to the SCN. Sleeping when the sun is up will not allow for the most restful sleep. The bedroom should be dark, or, as an alternative, a dark sleeping mask cold be worn.

Screens, especially mobile phone and computer screens, emit a high proportion of blue light. Avoidance of looking at screens before bedtime would be very beneficial for sleep onset and sleep quality. Alternatively, the program f.lux® could be utilised. It tracks sunset and gradually changes the colours of the light emitted by the computer and mobile phone screen, removing the blue light proportion at night. Also, blue light blocking glasses could be worn in the evening and at night.


Panda, S. (2007) Multiple Photopigments Entrain the Mammalian Circadian Oscillator. Neuron 53, 619-621.

Partch, C.L., Green, C.B., and Takahashi, J.S. (2014) Molecular Architecture of the Mammalian Circadian Clock. Trends Cell Biol.24(2), 90-99.

Tosini, G., Ferguson, I., Tsubota, K. (2016) Effects of blue light on the circadian system and eye physiology. Molecular Vision 22, 61-72.

The molecular regulation of the Circadian Rhythm

12.09.2016  /  Scienceandmore  /  Category: Plant Biology

The circadian rhythm was first mentioned by Franz Halberg in the 1950s. The term is based on the words circa, meaning “around” and diem or dies, meaning “day”. It refers to the 24 hour rhythm of living beings, mainly animals and plants.

Its outstanding characteristic is that it retains a 24 h rhythm without any cues from the environment that indicate the daytime. This means the circadian rhythm is generated within the organism (generated endogenously). Generally speaking, if a person for instance is in a completely dark room for an extended period of time, he or she would still have a daily rhythm of 8 hours sleep and 16 hours waking state.

What is it good for to keep track of time you might ask. With the help of the circadian rhythm animals and plants can anticipate reoccurring events and adjust to them. As an example, plants anticipate dawn and activate their photosynthesis apparatus, so light gets used efficiently as soon as possible. But the time of dawn changes with the season of the year and the rhythm has to be adjusted. Here environmental cues called “Zeitgeber” (time giver) come into play. These are signals such as the change of light intensity or temperature and with them the circadian clock adjusts to the correct time.

Circadian Rhythm in Plants

As suspected the circadian rhythm plays a much more important role for plants than it does for animals, as they are sessile organisms and cannot escape stress. They just have to deal with it. And again, anticipating stress and preparing for it can make a big difference when it comes to survival.

On a molecular level, the plant circadian rhythm’s center is the central oscillator that consists of a few genes that interact in a feedback loop with each other. A hypothesis has been established that depicts its regulation in a circuit called repressilator. This is a network where genes are expressed, (meaning a protein is synthesised with a gene as blueprint) during a certain time of the day and suppress (expression is prevented) the temporally preceding genes in the loop. Its important to understand that gene products, proteins, convey the actual function and that genes are just the blueprint for them.

For a better understanding of the central oscillator regulation, let’s forget about time for a moment. In the figure below you can see three gene clusters that are connected (clear) and the same gene clusters shifted (faint). We will concentrate on the clear part first. Here, the genes CCA1 and LHY suppress the genes ELF3, ELF4 and LUX, indicated by the blunt arrow. As these three genes are prevented from being expressed (and therefore their acting proteins not being present), they on their part cannot suppress the genes TOC1 and PRR5/7/9. As a result these four genes get expressed and their proteins suppress CCA1 and LHY. This again leads to expression of ELF3/4 and LUX, due to cessation of suppression by CCA1 and LHY. So in fact, the whole cycle is based on suspension of suppression.

Sounds complicated, but is is not. This mechanism could be compared to a circulation of three buttons, whereof one is pressed in (suppressed) and two are out (expressed). Pushing button 1, after a while, leads to pushing in of the following button 2, and hence coming out of button 1. Now the circle continues as button 3 is pushed in after a while and button 2 comes out. The circle closes when button 1 is pushed again and button 3 comes out.

Lets bring in time at this point. Therefore you have to look at the faint parts of the figure that show you the time of day when the respective genes are expressed. In the morning, CCA1 and LHY are expressed for a few hours and as they suppress ELF3/4 and LUX, these three genes are thereby suppressed in the morning. This results in suspension of suppression of TOC1, PRR5/7/9 and these four genes are expressed during the day toward the evening/night. Their expression again leads to suppression of CCA1 and LHY during the day, which therefore results to a gradual suspension of ELF3/4– and LUX-suppression. The three genes are subsequently expressed at night, during which they suppress TOC1 and PRR5/7/9. The circle closes by suspension of CCA1 and LHY suppression towards dawn, when they are expressed again.

Repressilator new

Scheme for the repressilator consisting of genes expressed at dawn (CCA1 and LHY), during the day (PRR9, PRR7, PRR5 and TOC1) and at night (ELF3, ELF4 and LUX). Lines represent repression of one gene cluster by the preceding gene cluster.

In this way the nine genes of the central oscillator regulate themselves and generate the circadian rhythm endogenously.

What do these genes of the central oscillator do but just regulate each other? During the time of their expression they are involved in the regulation of a lot of processes in the plant. In fact, the circadian rhythm partially regulates the already mentioned photosynthesis, as well as flowering and fruit production, and even the plant immune system. It was estimated that up to one-third of all genes of plants are partially controlled by the circadian rhythm, showing the importance of this mechanism!


L. Harmer, S. Panda and S. A. Kay (2001): Molecular Bases of Circadian Rhythms. Annu. Rev. Cell Dev. Biol. 17:215-53
Smith (2000): Phytochromes and light signal perception by plants- an emerging synthesis. Nature 407:585-91
Pokhilko, A. P. Fernández, K. D. Edwards, M. M. Southern, K. J. Halliday and A. J. Millar (2012): The clock gene circuit in Arabidopsis includes a repressilator with additional feedback loops. Mol Syst Biol. 8:574
Huang, P. Pérez-García, A. Pokhilko, A. J. Millar, I. Antoshechkin, J. L. Riechmann, P. Mas (2012): Mapping the Core of the Arabidopsis Circadian Clock Defines the Network Structure of the Oscillator. Science.336:75-79G.
McWatters and P. F. Devlin (2011): Timing in plants – A rhythmic arrangement. FEBS Letters. 58:1474-84