Defining circadian rhythms
Circadian rhythms refer to the roughly twenty-four hour cycle of our body’s physiological processes. The word circadian comes from latin (circa, meaning “around” or “approximately”, and diem meaning “day”). Circadian rhythms are found in virtually all life on the planet, from bacteria and plants to insects and mammals. Not only are they present across all species, but every cell in our body follows a circadian rhythm. These rhythms govern when a cell is most metabolically active, when hormones are produced, when repair processes are activated and more.
Life on earth has evolved under the conditions imposed by the earth’s rotation around the sun. This rotation causes predictable and profound changes in environmental light, temperature, and food availability over the course of each twenty-four hour cycle. Organisms that effectively anticipate these changes by way of their circadian clocks, and optimize their physiology and behaviour accordingly, have a major advantage over competitors and predators.
Unfortunately for us humans, we are biologically prepared for a world that no longer exists. Since the close of the industrial revolution, we have become ever more separated from our environment. If you’re reading this, you live in a world with twenty-four hour access to light, food, and control over temperature. We are no longer at the mercy of the day/night cycle for being productive and we can travel across multiple time zones in a matter of hours.
This level of control is obviously a net positive for the human race, but it has happened at such a rapid pace that our biology has been unable to keep up. Our circadian rhythms are the product of 3.5 billion years of evolution, whereas widespread control over our environment extends back less than one hundred years. Expressed as a percentage, this represents about 0.00000003 % of our evolution from single cell organisms.
I was going to include a pie chart to illustrate just how small a period this is in respect to our evolution, but even when changing the numbers to reflect the 2.8 million years of human evolution only, the slice was still too small to see.
In order to manage this mismatch between our current environment and the one in which we have evolved, a basic understanding of the circadian system is necessary. We must learn to nurture our rhythms, as they control every key aspect of biochemistry, physiology and behaviour.
What are circadian clocks?
A circadian clock is a biochemical oscillator that controls the timing of circadian rhythms. Every organ, tissue and almost every cell in the body has a circadian clock.
The master clock
Humans, and all other mammals, have a master clock which coordinates all the different rhythms in the body – the suprachiasmatic nucleus (SCN). The SCN is located in the brain, at the base of the hypothalamus. This location is important because the hypothalamus regulates hunger, thirst, sleep, body temperature and important aspects of behaviour – all of which exhibit a distinct circadian rhythm.
Peripheral clocks
Refer to clocks other than the SCN that are located in organs and other tissues. Although the SCN plays a role in synchronizing and coordinating rhythms in the periphery, it doesn’t maintain them. Circadian rhythms have been shown to persist in lungs, livers, and other tissues grown in a culture dish, isolated from the SCN.
Clock timing
Circadian rhythms are generated inside the body and are self-sustaining – meaning they will persist even under constant environmental conditions. This has been shown in human studies where subjects kept in constant darkness for long periods of time still show clear daily patterns of sleep and activity[1].
Unfortunately these self-sustaining clocks operate on a cycle that is not exactly twenty-four hours, with most humans having slightly long body clocks (twenty-four hours and fifteen minutes on average). When under constant environmental conditions, as in the study above, the clock will free-run, with the patterns of sleep and activity occurring slightly later, or earlier each day, depending on the length of the individual’s body clock. For this reason, the clocks need to be “set” each day so the body stays synchronized with the external environment.
Setting the clock
The process of “setting” the body’s clock so that rhythms are synchronized to the cycles of the environment is called entrainment. The entrainment process is accomplished through the use of external cues known as zeitgebers (a German word meaning “time-givers”). Light is considered the primary zeitgeber but there are others as well – food intake, temperature, activity/exercise, social interaction, etc. The body is constantly using these external cues to entrain the clock so behavior and physiology are optimized, and free-running is prevented.
Entrainment is a slow process
The body takes a long time to adapt to rapid environmental changes. This makes sense from an evolutionary perspective, as changes in day length occur slowly with the seasons, and it would take many days for a human to cross even one time zone.
The time it takes for entrainment has only become a problem in recent years. Air travel has enabled us to fly half-way around the world in a single day and artificial light has lead to round the clock production and services. Unfortunately it generally takes about one day for our internal clocks to adjust for each hour of circadian disruption (i.e. one day per time zone crossed or one day per hour change in schedule, in the case of shift work).
Let’s say you’ve been working a string of twelve-hour day shifts (07:00 – 19:00) and are now switching to nights. At eleven o’clock that first night, your biological clock will be telling you it’s time for sleep, meanwhile you still have eight hours left in your shift, plus a commute home. It will likely take a week or more before your internal clock adjusts – if it adjusts at all.
Entrainment to the light-dark cycle
So how does the entrainment process happen? Since light is the most reliable zeitgeber, we will use it as an example.
Changes in both light intensity and spectrum are detected by a light-sensing protein in the eye called melanopsin, and this information is relayed directly to the SCN via optic fibres. These changes help synchronize the master clock to the day/night cycle.
One notable example of how the SCN uses this information is coordination of the body’s melatonin cycle. Melatonin production starts shortly after nightfall, when the eyes are detecting very little light. The release of melatonin signals to the body that it is time for sleep, producing drowsiness. As the night progresses, melatonin continues to rise, reaching peak concentrations around three or four in the morning. Levels then start to fall, and when the eyes detect light – even through closed eyelids – melatonin release is shut off, signaling to the body that the sleeping period is over.
Zeitgebers at “unnatural” times can cause phase shifts
Circadian rhythm phase shifts happen when external cues cause a rhythm to begin earlier or later than normal. One of the most obvious examples is when we are exposed to artificial light at night. Suppose you go grocery shopping at nine p.m. to avoid crowds. These stores can have lighting of up to 1000 lux – more than enough to suppress the release of melatonin and cause a phase shift in your circadian clock[2].
Light exposure timing determines direction of phase shift
Light exposure around dusk and during the early part of the night causes a phase delay (rhythms occur later than normal) whereas light during the later part causes a phase advance. In the example of melatonin, when subjects are exposed to light in the later part of the night, peak levels occur earlier than they would have had the rhythm not been shifted[3].
Light intensity affects entrainment
In today’s society, it’s not uncommon for individuals to spend the entire day indoors, where light intensity typically ranges from 150 to 500 lux. Sunlight on the other hand can produce more than 100 000 lux of light on a sunny day. Even overcast days produce over 1000 lux. This lack of light exposure during the day will cause you to be more sensitive to the phase-shifting effects of light at night[4]. This is why experts on circadian rhythms advocate for both avoiding bright lights after dark, and getting adequate sunlight exposure during the day.
Entrainment of peripheral clocks
As mentioned above, the SCN takes its cues from the light-dark cycle and then sends synchronizing signals to peripheral clocks. The “master clock” status of the SCN is why light is considered the primary zeitgeber. However most peripheral clocks, including the ones in adipose tissue, gut, liver, muscle and pancreas, use food intake as the primary zeitgeber[5].
Zeitgebers ability to entrain rhythms is variable
Under unnatural conditions, the power each zeitgeber has to entrain rhythms is not consistent. As an example, when food consumption is erratic, or constant, the SCN will use light cues more readily to compensate. Conversely, when under constant or near constant lighting conditions, food intake will have greater entraining abilities[6].
Overriding the SCN under conditions of weak or erratic light signals is a protective mechanism to allow the animal to avoid starvation.
Clocks can become desynchronized from one another
There are many instances where the clocks will uncouple from one another. One prime example is when animals are subjected to weak or erratic lighting signals as mentioned above.
In a study looking at night shift work, the sleep schedule, meal times and light/dark cycle of the subjects were all shifted by ten hours. The researchers found that this did not result in uniform phase shifts among different rhythms. Rhythms in peripheral cells were entrained to the new schedule after as little as three days, whereas rhythms under the influence of the SCN, such as melatonin and cortisol, took three times as long to adapt (nine days)[7].
Note: These last two points have important implications for shift workers and frequent travelers, since lighting conditions are often out of their control. Meal timing strategies can be used to help compensate for the disruption imposed by the altered light/dark cycle and sleeping patterns.
How does the SCN communicate with the rest of the body?
Coordination of the body’s rhythms by the SCN is a complicated process and the exact mechanisms through which this occurs remain unknown. Though it is known to involve neural communication and actions involving hormones in the blood[8]. The SCN also receives feedback signals from the periphery which allow the whole body to function in harmony.
What is circadian disruption?
This overview should provide some insight into how circadian rhythms become disrupted. Not only can the SCN become desynchronized with the external environment, but clocks in the periphery can become uncoupled from the SCN as well.
Though not covered in this article, it should be noted that genetic factors (polymorphisms or mutations in circadian rhythm genes) can also contribute to circadian disruption[9].
What is the impact on health?
There is a slew of negative health conditions associated with circadian disruption, and more evidence is constantly being uncovered. Conditions include increased risk for premature death, cancer, metabolic syndrome, cardiovascular dysfunction, immune dysregulation, reproductive problems, mood disorders, and learning deficits[10].
Conclusion
The circadian system is highly complex and there is much more to be discovered. But with this basic knowledge in hand, you can start to make better decisions toward minimizing circadian disruption.
References:
- https://www.ncbi.nlm.nih.gov/pubmed/5813435
- https://physoc.onlinelibrary.wiley.com/doi/full/10.1111/j.1469-7793.2000.00695.x
- https://pubs.niaaa.nih.gov/publications/arh25-2/85-93.htm
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6212492/
- https://www.ncbi.nlm.nih.gov/pubmed/30650649
- https://doi.org/10.1111/j.1460-9568.2009.06959.x
- https://academic.oup.com/sleep/article/30/11/1427/2696874
- https://pubs.niaaa.nih.gov/publications/arh25-2/85-93.htm
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4632990/
- https://www.ncbi.nlm.nih.gov/pubmed/23899601