Nobel Prize winners unmask our inner timekeeper

This winning discovery brings us closer than ever to understanding our body clock…

Written by: Carys Green

Art by: Sotiria Kal and Sia Agarwal

Humans have evolved to follow a daily routine governed by the sun; we wake when it rises and tire when it sets, in a 24-hour cycle. It has long been known that this is due to our very own biological clock, also known as the circadian rhythm. This is a mechanism that governs how our bodily functions work depending on the time of day, controlling our sleep cycle, hormone levels, body temperature, metabolism and even our behavior. Despite its importance in keeping our bodies in check throughout the day, its mechanism has only ever been speculated. However, this year’s Laureates of the Nobel Prize for Medicine have solved the puzzle.

The Nobel prize was jointly awarded to three American scientists; Michael W. Young, Michael Rosbash and Jeffrey C. Hall for identifying the mechanism behind the circadian rhythm in our bodies, ‘explaining how plants, animals and humans adapt their biological rhythm so that it is synchronized with the Earth’s revolutions’, as commented by the Nobel Committee. They have proved what has long been hypothesized, that this clock is in fact endogenous in all multicellular living organisms.

It all began with previous research conducted in the 1970’s, when researcher Seymor Brenzer isolated an undiscovered gene in fruit flies, which he named Period. On silencing this gene in the fruit flies, it appeared that they no longer followed the same circadian rhythm. Their behavior and bodily functions were out of sync with the time of day, suggesting that this gene somehow controlled the flies’ own biological clock. Further research was needed to determine just how this body clock ticked and this year’s Nobel Laureates did exactly that.

Continuing to work on fruit flies, Hall and Roshbash established that the Period gene encoded a protein, named PER, which followed an oscillatory effect. It accumulated during the night and then depleted its levels during the day, regulating itself and hence the physiology of the fly over a 24-hour period. Separately, Hall then went on to discover two more genes that were necessary for the workings of Period, ensuring the fluctuating levels of PER followed the same rhythm every day. Over the years they went on to further illustrate the inner workings of the clock, identifying the involvement of more proteins and in particular ‘the mechanism by which light can synchronize the clock”’, as the Nobel committee highlight. These molecular mechanisms are now known to be present in most cell types in multicellular beings, all working complementary to one another.

Since our circadian rhythm is pivotal to how our organs and critical processes such as our metabolism work corresponding to the time of day, its maintenance is pretty important. With it we feel tired at the right times of the day to sleep at night, our digestion and eating habits are regular, our body temperature is kept constant and so on. So what happens when the clock is disrupted? A misalignment between our internal clock and our anticipated external environment can cause havoc to our well being, as commonly demonstrated in humans by ‘jet-lag’, where our body clocks are not in sync with local time. However, as stated by the Nobel committee, research shows that repeated disruption to our circadian rhythm could cause an ‘increased risk for diseases’. The National Institute of General Medical Sciences (NIGMS) point out that ‘irregular rhythms’ due to lifestyle choices have been linked to numerous chronic health conditions, such as ‘sleep disorders, obesity, diabetes, depression, bipolar disorder, and seasonal affective disorder.’

As light is one of the main influencing factors for the regulation of our circadian rhythms, there are numerous studies aiming to understand this interaction better. Researchers such as those at Douglas Mental Health University Institute (DMHUI), are currently studying how late night shift workers may have their sleep-wake cycles altered. At DMHUI they have found evidence that ‘circadian misalignment’ has lead to ‘multiple hormonal and metabolic disturbances’. They propose this could negatively affect the physical and mental health of these workers. Several groups are also testing how severely light from the use of electronic devices during the night disrupts our circadian rhythms and therefore our overall wellbeing. Many health organizations have addressed concern over this issue including the American Medical Association (AMA) who published a warning report entitled ‘Light Pollution: Adverse Health Effects of Nighttime Lighting.’

The American scientists have been awarded this year’s Nobel prize, not only for enlightening us with their exceptional mechanism, but also for the expected implications this discovery has for medical health. The discovery of the mechanism has created an upsurge in the field of chronobiology, the study of circadian rhythms. One example of ongoing research is the investigation into whether the workings of a drug can be optimized, or unwanted side effects removed, if it is taken at a specific time of day, when the medication conforms well with the patient’s body clock. Outside of medical research, this idea can be extended to determine the best time of day to exercise or even to study. The complete mapping of the circadian rhythm mechanism could potentially give rise to an exciting, leading scientific discipline that has the answers to many challenging medical problems. Furthermore, as this research confirms the importance that light plays in the upkeep of our body clocks, it could lead to important changes in the way we live as a society.

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