The Body Clock – What Makes Us Tick?

Have you ever wondered why a lot of our body’s processes follow regular daily rhythms? In 2017, the Nobel Prize for Physiology and Medicine went to scientists who were investigating just that. US Scientists Jeffrey Hall, Michael Rosbash and Michael Young discovered the innate mechanisms that allow our bodies to act in regular cycles throughout the day. As the earth is governed by 24-hour cycles of temperature and light, It’s occupants have evolved their own methods of detecting these cycles and synchronising their behaviours in response. This is demonstrated through the human sleep wake cycle corresponding roughly with the hours of daylight or how plants have the ability to adjust their leaf positioning in anticipation of the sunlight.

 

So how has the human body adapted in response to the 24-hour day?

Within nearly every cell in the human body, there is a molecular clock mechanism which controls the rhythmic actions of the individual cell. This allows specific tissues to regulate functions such as glucose release and fat storage throughout the day. These cell-based clocks are ultimately synchronised to a ‘master clock’, which is present within the hypothalamus of the brain. The area of the hypothalamus that is responsible for generating circadian rhythms is known as the suprachiasmatic nuclei (SCN). This is a wing shaped structure, containing thousands of neurons, which are capable of receiving signals from the body’s sensory functions. This allows for the input of information from our environment. For example, the surrounding light intensity is observed via the eye and conveyed to the SCN.  External cues that are able to have an effect on the body clock are known as Zietgebers. These are used by the body to ensure that it’s 24-hour cycle is synchronised to that of the Earth.

 

The Underlying Mechanism

Within the cells of the SCN, these 24-hour clocks are produced by cyclic patterns of gene expression. In a simplified model, two proteins known as CLOCK and BMAL1 bind together. This promotes the expression of genes called PER and CRY so that transcription can occur, ultimately resulting in the production of their protein products. Once the PER and CRY proteins are produced, they will then bind together and inhibit CLOCK and BMAL1, stopping the production of PER and CRY proteins. Eventually, the existing PER and CRY proteins will breakdown and no longer be able to inhibit CLOCK and BMAL1. Once this has occurred CLOCK and BMAL1 are free once again to bind together and restart the process. This whole cycle takes approximately 24 hours. As PER and CRY proteins are responsible for preventing their own transcription, this is a form of negative feedback. As this cycle is not exactly 24 hours in duration, regular input from Zietgebers is required in order to maintain synchronicity between the internal clocks and the external cycles. The SCN can then adjust the synchronisation of the clocks throughout the body via either hormones or the autonomic nervous system. Experimental evidence demonstrates that when humans are isolated from any Zeitgebers, their circadian rhythms remain approximately 24 hours long but will gradually drift away from the that of the Earth.

 

Controlling the sleep cycle

Alongside acting as a Zeitgeber, light also has the action of suppressing the activity of the pineal gland, preventing the release of the hormone melatonin. Melatonin is a sleep promoting hormone that has a key regulatory role in the circadian rhythm of our sleep wake cycle. Melatonin is secreted at its maximum levels overnight and will then begin to decrease when the stimulus of light is introduced. Although other hormones and factors can contribute to when we feel tired, such as the build-up of  adenosine in the brain over the time we are awake, melatonin is responsible for promoting the daily sleep rhythm. Therefore, when we encounter light outside of the natural daylight hours, this can disrupt our sleep cycle. This can be seen in people who work night shifts as their circadian rhythm often wont fully align with being awake at night and sleeping during the day. To combat this, they may be recommended to either take melatonin supplements in preparation for their sleeping hours or use an artificial light box at the start of their day to inhibit melatonin release. The disruption of melatonin levels by irregular light patterns is also why we experience jet lag after travel and the reason behind the introduction of the ‘Night Shift’ feature which alters the light that our phones emit in the hours before we go to bed.

 

Is the modern working day in our nature?

Although circadian rhythms have evolved as a way for us to adapt to the Earth’s natural cycles, they can often clash with modern life. Alongside the problem of artificial light disrupting melatonin cycles, early mornings for either work or school can often result in us having to wake up too early in our cycle, leaving us lethargic. Many people will then try to compensate for this lack of sleep by waking up later on the weekends, which further disrupts the cycle. This is sometimes referred to as social jetlag. This raises the interesting question: should modern working days change to fit our circadian rhythm?

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