Ever wondered how our body ‘knows’ to get tired at night, and feel full of energy in the morning? This body clock is determined by circadian rhythms, and can be disrupted by our behaviour and disease. Photo credit: bruce mars via Unsplash
We’ve likely all felt it: hyper-alertness after looking at our phones or that extra hour in bed making us groggy all day. Fatigue is so common that we cannot go a day without feeling it ourselves or having someone we know complain of it. For someone like myself who deeply enjoys early mornings (and suffers from the idea of waking up late), the phenomenon of the “body clock” is fascinating. For years, we have known about bodily cycles and how they culminate in our rest-wake periods, but the underlying chemical mechanisms are less widely discussed. Therefore, let’s explore our subconscious — and the things that make it tick.
Biology of the Clock
Our “body clock” is based on a phenomenon called circadian rhythms, which govern physical and mental changes over the course of the day. While primarily governed by exposure to light and darkness, these rhythms are kept in check by a region of our brains called the hypothalamus. Here, we find the suprachiasmatic nucleus (SCN): an area that is directly aligned with the eyes and so receives signals corresponding to “night” and “day”. For example, the SCN is the reason why we start to feel so sleepy in the winter at 4 pm, when in the summer, we are still active, alert, and energised (which perhaps does not bode well for students). These feelings of wakefulness are explained by the production of the chemical melatonin, which is influenced by the SCN in response to reduced light.
Our “body clock” is based on a phenomenon called circadian rhythms, which govern physical and mental changes over the course of the day.
The extreme living conditions found at the North Pole emphasise the importance of the hypothalamus’ contribution. Here, human populations are exposed to 24-hour sunlight in the summer with gradually less daylight over time, culminating in perpetual darkness during the Winter Solstice. Despite this, these people do not stay awake throughout the entire Summer. While obtaining sufficient sleep is difficult, the use of black-out curtains and melatonin supplements by researchers and explorers helps in retaining a functioning body clock. This emphasises that, while light plays a significant role in regulating circadian rhythms, they are also sustained by chemical factors that can override light signalling when necessary.
Despite what we may think, studies have shown that wakeful signals are actually strongest in the evening. This can be explained by a simple analogy. As the day goes on, we have gone longer and longer without sleep. Hence, our brains need to produce more wakefulness signals to keep us going for the duration of the day. This is known as a wake duration-dependent model and explains the wakefulness “kick” that many of us experience in the evenings.
Notably, there are genetic factors controlling circadian rhythms, too. The genes “Period” and “Cryptochrome” code for “wakefulness” proteins — the amounts of which build or drop depending on body clock progression. Indeed, the levels of these proteins can be influenced by altered exposure to light (such as a computer screen), resetting our body clock. In some situations, an altered clock is beneficial — people on shift work may need to be alert at 2 am and sleep at 1 pm. In others, however, mutations in the aforementioned proteins, or even diseases such as diabetes and depression, can be detrimental to our clocks. For example, it has been shown that diabetics have atypical circadian oscillations in hormones such as cortisol. This not only impacts sleep but also influences the production of molecules involved in bone formation and decreases cellular insulin sensitivity. It is therefore important to recognise that disrupted circadian rhythms can affect wider factors than just our sleep, such as the regulation of body temperature, digestion, and hormone release. All of these are essential elements for good health, so studies into this area are integral to general healthcare.
In addition, whether we are an early bird or a night owl may be determined by our genes. A study conducted on a volunteer basis, in which subjects underwent a cheek swab, showed that those who had reported being early risers had similar genetic profiles to other self-reported early risers. The case was the same for the night owls. In fact, the aforementioned gene “Period” has a role in determining which camp someone falls into, alongside 350 other genes.
So, what about our everyday lives? In our modern society, with its busy schedules and work-play attitude, it is not surprising that as many as 2.25 billion cups of coffee are consumed worldwide per day. While hailed for its ability to keep us awake, caffeine also has negative impacts on our natural circadian rhythms. Studies in mice and mammalian cells have revealed that caffeine consumption causes delays in our “body clock” cycle. Essentially, this amounts to falling asleep later than our bodies would naturally desire. This has a knock-on effect due to the necessity of getting up early in the morning, impacting sleep duration and quality. This condition is particularly prevalent in students.
Interestingly, optimal sleep duration was found to be highest in student populations rather than in older adults, as one may expect. In fact, when tested at pulling an “all-nighter”, it was actually the elderly test subjects that fared better. Unfortunately for many people, it has also been shown that it is extremely difficult to make up for lack of sleep. Indeed, research has suggested that even for one hour of “sleep debt”, to compensate, someone would need to gain adequate rest for four days straight. Therefore, it becomes (mathematically) extremely unlikely to compensate for lost hours in the week, even with a long weekend lie-in. Nevertheless, those who sleep little during the week may reduce their risk of cardiovascular disease if they sleep in at the weekend when compared to those who have minimal sleep throughout the entire seven days. This is just one of the intricacies seen in sleep research, suggesting that the process is much more complex (and potentially subjective) than we have yet to discover.
Another commonality of student life is the computer screen. We all know it — we shouldn’t look at our screens before bed as the blue light keeps us awake. Intriguingly, though, it has been discovered that even our room lights, which we likely switch off at the moment of settling for the night, keep our clock in “wakeful” mode. This reveals the supreme sensitivity of the circadian clock.
The Clock in disease
By investing in research into the chemistry behind circadian rhythms, we can begin to target them to enhance human health in various ways. For example, melatonin communicates to multiple organs that it is dark by blocking “wake signals” in the SCN, inducing ‘night-state physiological functions’. In addition, the chemical acts at direct mode network (DMN) regions of the brain, which are active during periods of rest. Aberrant melatonin levels have been implicated in several sleep disorders, as well as in the early stages of Alzheimer’s disease. Therefore, the use of it in relevant therapies could be revolutionary, and placebo-controlled trials have already shown promising results.
By investing in research into the chemistry behind circadian rhythms, we can begin to target them to enhance human health in various ways.
Studies have noticed a correlation between dementia case progression and disordered sleep. Even in healthy individuals, it has been shown that people suffering from sleep apnea — where breathing stops and starts during sleep — are more at risk of developing dementia later in life. In dementia patients, disturbed sleep patterns, such as several naps throughout the day, may have a self-perpetuating effect: the more irregular the circadian rhythms, the worse the brain can function the next day, which causes worse wakefulness regulation. Indeed, observation of dementia patients has revealed that on days when they had a better night’s sleep, their cognition was comparatively better than the day after a bad night.
This raises questions as to whether we can intervene in this vicious cycle. Thus far, research has highlighted bright light therapy as a potential treatment for disturbed sleep in dementia patients. This method involves the patient sitting in front of a light box that emits light approximately 30 times brighter than a room light for set periods in the day. Significantly, a small study showed improved restfulness and sleep patterns in patients who had undergone this treatment.
Alternatively, “photobiomodulation” involves a headset that transmits near-infrared light into the brain. The goal here is to ‘change the way the brain reacts to the damage that can lead to dementia’. Excitingly, although conducted in only a few participants, this therapy increased cognition, reduced anxiety, and eased sleep in all patients involved. Ultimately, this is a promising development in the field of dementia treatment.
The Future of the Clock
When researching this topic, I came across an infographic that depicted how to maintain a healthy circadian clock. The tips were as one would expect, highlighting how activities that contribute to other elements of health, such as exercise, getting sunlight, and a consistent sleep schedule, are integral to keeping our “body clocks” in good shape. As more and more is discovered regarding circadian rhythms, the more apparent it becomes how this system greatly impacts our health. Applying these findings in the clinic will be key to bettering the treatment of general health and disease, leading us to new horizons over which to count our sheep.