The Biology of Time: Circadian Rhythm

Photo by  DAVIDCOHEN  on  Unsplash

Photo by DAVIDCOHEN on Unsplash

Author: Senija Selimovic-Hamza Edited by: Eleonora Lugara

There is no perfect time to write such an article. Or is there? Long before we started organizing life in fancy planners and living by external watches and calendars, it was possible to use time wisely and get things done. Animals, plants, even bacteria – none of these are faithful customers of the Swiss watch industry, but they know exactly when to do what. But how ? All forms of life on our planet are adapted to following the rotation of the earth and the daily changes of the environment unconsciously, by using inner clocks.

In the 1980s three scientists went on the hunt for genes which might be responsible for controlling the inner clock in fruit flies and characterized a gene named “period”. Period encodes for the protein PER that is synthetized during the night and degraded during the day. The complex signaling cascade of which PER is part of, triggers a negative feedback loop which sets the alignment of the light/ dark cycles in mammals and invertebrates. For identifying additional factors of genetic time-regulation , they started obtaining multiple awards. In 2017 these inner clocks became popular when the Nobel Assembly at the Karolinska Institute in Sweden finally awarded the Nobel Prize to these three scientists, i.e. Jeffrey C. Hall, Michael Rosbash and Michael W. Young, for their discoveries of molecular mechanisms controlling the circadian rhythm.  Long before this had happened, an astronomer named Jean Jacques d’Ortous de Mairan had already decided to study day-night rhythms of mimosa plants. These plants usually close their leaves at night, but open and orient them towards sunlight during the day. It was in the 18th century when de Mairan found out that even if mimosas were placed in darkness for several days, they would open their leaves at the time the sun would rise and close them for the sunset, indicating there must be a time-mechanism in these plants.

Being on time is not only a professional attitude - it is a life saver. Plants which rely on photosynthesis would starve if they slept through the day. The same is valid for small and simple organisms consisting of only a few cells. They need to know that there are times when the sun could burn them to death and eventually discern how and when to avoid it. These dangers affect vertebrates ,including us humans, just as much as all smaller living beings that rely on circadian clocks. Sleep regulation may be the most logical and obvious manifestation of the circadian rhythm, but by far it is not the only one. Ovulation, digestion, memory function and so on are all essential processes rely on good timing mechanisms, and each disconnection from the inner clock could potentially trigger a disease. Circadian disruptions have been examined for a while now and the consequences can vary, ranging from inducing the annoying jet lag to affecting the normal aging process. The more damaging effects are obesity, infertility, neurological disorders (like Alzheimer’s or dementia), and even the development of cancer. As each cell and each organ system seems to have its own peripheral clock kept in coordination with one big central clock, there are many potential targets for the development of pathologies.

That inner, central time-keeper is an area of the brain called the “suprachiasmatic nucleus”.  It relies on sunlight, namely the blue end of the visible spectrum. The eyes will, for instance, sense the change in light from the outside and send a signal to the brain that it is getting dark. The brain will then forward this signal to the body to release melatonin, which will make the body feel tired and prepare it to relax and eventually fall asleep. In a healthy state this cycle is synchronized with the natural appearance of light, and can therefore calculate the timing to keep the peripheral clocks ticking correctly. A disruption of this system, meaning too much of light during the night, or too little during the day, and the clock loses its beat. Skipping a beat is thereby expected in a world full of artificial lights. Our lives have changed in terms of lifestyle. While our ancestors were mostly sleeping during the night, nowadays people have night shifts, they travel across time zones - they support the circadian disruption unconsciously.

Photo By: Steve Thompson, AFMS Public Affairs

Photo By: Steve Thompson, AFMS Public Affairs

In a recent study in the UK, 90,000 participants were given accelerometers on their wrists and their movements were measured in order to detect circadian disruptions such as restless sleep. In addition to this, they were asked questions about their mental health. The researchers concluded, that the more the circadian clock is off beat, the more likely people are to have major depression disorders or bipolar disorders, mood swings or neuroticism. They showed lower levels of satisfaction with their health state and lower levels of happiness. Shockingly, people with a high circadian disruption, seem to have a slower reaction time, which can have a dramatic effect on the lives of others in scenarios where a fast reaction is crucial, such as when driving.

Sleep disorders, as one form of the circadian disruption, have been rising constantly in the last years. In 2017, BBC reported that the NHS has registered 147,610 sleep diagnostic tests in the year before; this is a dramatic shift. During 2007-2008, only 69,919 people sought medical help for sleep disorders. Whoever has experienced insomnia at least once, will not be much surprised that the treatment of circadian disruptions has become a business worth billions. The urge to regulate the inner clock and make it work again is growing along with the wellness and healthy-living trend, but this one is also showing a great medical relevance. Many gadgets aiming to help get back your perfect inner timing are on the market and many more are to come. The desperation because of restless sleep drives people to take pills or plasters of melatonin, use apps and sleep trackers, buy new beds and mattresses; we are willing to try it all and we are obsessed by it. The bestseller list of Amazon highlights this obsession; the ultimate bestseller in the last few years is a children’s book called ‘The rabbit who wants to fall asleep’. Normal, healthy sleep has become everything else than norma. It has become a luxury item and a trending topic.

Yet, there is another perspective beyond the concern about diseases caused by circadian disruption. Now that knowledge on the circadian rhythm is increasing, it is opening up new possibilities for making good things even better. Science suggests that bright, blue-rich light during the day increases our concentration and energy levels, while warm, soft hues in the evening may help us feel tired when it is about time. These findings can be used in schools and universities, where lights which mimic the rising of the sun can change the learning experience for the better. This phenomenon, known as ‘human-centric lightning’, is becoming increasingly popular all over the world and installations of such lightning are increasingly prevalent not only in schools, but also in office buildings or sports arenas. Many subjective reports from people who work in such settings are available online and the results of mimicking natural light by using LED-lamps appear convincing, not only because of making people feel better, but also for saving energy.

Changing the infrastructure of lighting may thus become a public health issue in the near future, although we may not yet have enough knowledge on the circadian rhythm to prove all these concepts to be right. However, the technology for such changes is already in our hands. Scientists are producing new findings on a daily basis, and most importantly, we have finally understood that if we go back in time with our habits, we might finally start being on time.