‘Early to bed and early to rise makes a person healthy, wealthy and wise.’

This is a very old saying that all of us have heard from our elders. The true essence of it can be
understood only when one knows about the natural clocks, also called the circadian clocks
present in our body.
The circadian clock is a controller of all sorts of biological processes which follow a 24 hour
cycle. These processes include brain-wave activity, sleep-wake cycles, body temperature,
hormone secretion, blood pressure, cell regeneration, metabolism and behaviour. The circadian
clock of mammals and humans have a central clock and numerous peripheral clocks in the
tissues. The central one is the master clock, also called the circadian pacemaker, which is
present in the suprachiasmatic nucleus(SCN) located in the hypothalamus of the brain. This
master clock is influenced by environmental cues, especially light. This master clock
synchronises the functions of the other peripheral clocks. Among the various circadian rhythms, the sleep wake cycle is a very important one.

Significance of circadian rhythm:

●This rhythm is important for maintenance of good, restorative sleep. A good sleep helps us to be safe while performing various activities, like driving, cooking etc.
● It regulates release of hormones that are responsible for various vital functions in the
body.
● It is significant for metabolic activities of the body, especially lipid metabolism. It also
plays a role in thermogenesis and energy homeostasis.
● It is also essential for neurodevelopmental processes.

Factors regulating the circadian rhythm:

The human clock is generally longer than 24 hours. There are regular cycling environmental cues that entrain it to be 24 hours. These factors called zeitgebers, are external time giving cues which include:

Light – For the circadian rhythm, light is the strongest entraining agent. Information about the light-dark cycle is relayed from the retina to the SCN. This is done primarily via the retinohypothalamic tract which is a neural pathway distinct from the visual system. The timing of light exposure is extremely crucial. It determines its ability to bring about changes in the timing of circadian rhythms. In humans, exposure to bright light in the early morning induces phase advances, whereas light exposure in the evening delays the phase of circadian rhythms.
Temperature – There is a close relation between the circadian cycles of sleep and temperature.
Sleep is majorly initiated in the evening when the core body temperature(CBT) declines. By the
next morning, this temperature reaches its minimum and then starts rising again. This is when
our major sleep period ends. Our CBT is lower when we are asleep as compared to when we are awake. Body temperature nadir is reached around one and half to two hours before sleep
timing. If this is somehow altered, it affects the onset of sleep as well as awakening from sleep.
Hormones:
Melatonin – It is less effective as compared to bright light, but it has circadian phase
shifting properties. The SCN regulates the timing of melatonin release from the pineal
gland. Its secretion is suppressed by exposure to bright light. The levels of endogenous
melatonin begin to rise approximately 2 hours before sleep onset. It remains elevated
during the habitual sleep hours and is responsible for the circadian expression of various
clock genes.
Cortisol – This hormone keeps us alert and active and is released more during the day.
Exposure to light in the night can also trigger its release instead of melatonin.

There are genetic factors that regulate circadian rhythm :
At the molecular level, the circadian rhythm is regulated by a transcriptional feedback loop. This loop consists of two components:

Positive limb – These include the genes Clock and Bmal1
Negative limb – It consists of Per (Per1 and, Per2) and Cry (Cry1 and Cry2) genes.

The CLOCK:BMAL1 heterodimer initiates the transcription by binding to specific DNA elements,
E-boxes (5′-CACGTG-3′) and E′-boxes (5′-CACGTT-3′) in the promoters of target genes. This
activates the Per (Per1 and, Per2) and Cry (Cry1 and Cry2) genes. These produce the proteins
PER and CRY respectively. These proteins bind to the CLOCK:BMAL1 heterodimer bound to the
E-boxes and inhibit them from further activation of Per and Cry genes. Once the PER and CRY proteins are degraded, the CLOCK:BMAL1 heterodimer can once again promote the production
of Per and Cry genes.

Conditions that can disrupt the Circadian Rhythm:

Jet lag – This condition generally arises when a person travels to different time zones. It is
generally experienced by people who take intercontinental flights. The effect continues until a
person is able to adjust with the day-night timings of the new place.

Shift Work Disorder – A number of jobs these days are such that it requires people to work
through the night or up till late night. This severely disrupts their sleep wake cycle as they sleep
during the daylight hours.

Light from electronic devices at night – White light is made up of seven colours. Out of these,
blue light is the most detrimental to sleep. Exposure to blue light emitted from fluorescent and
LED lights, screens of tablets, computers, mobiles, etc. during the sensitive periods trigger the
photoreceptors in the retina to send signals capable of suppressing the release of melatonin.
This causes a major shift in circadian rhythm.

Delayed sleep phase disorders(DSPD) – This is associated with people who tend to stay awake
late in the night(night owls) and sleep till late in the morning. It generally affects 0.1 or 0.2% of
the population but impacts upto 16% of teens. It presents itself as sleep onset insomnia and
sleep sets in between 2 to 6 AM and one is not able to wake up on time for work, school, etc.
Genetic mechanisms may also play a role. For example, the DSPD phenotype has been
associated with polymorphisms of the circadian genes, Clock and Per3.

Non 24 hour sleep wake disorder – Blind people are mostly affected by it as they do not receive
the light cues in their circadian rhythm. Their body still follows the 24 hours rhythm, but their
timing of sleep keeps shifting by hours or minutes.

Irregular Sleep-Wake Rhythm Disorder – These patients do not have a pattern of sleep. They
have numerous short naps in 24 hours. This condition is associated with various conditions that are injurious to the brain such as dementia, traumatic brain injury, etc.

Genetic mutations – Mutations in the CRY and PER gene are mainly known to be responsible
for a non-aligned circadian rhythm. If their proteins are not well expressed it leads to many
sleep related disorders.

Impact on the body and health:

Sleep disorders – Sleep disorders due to disturbance of the circadian clock are often not
diagnosed, but these can lead to severe cognitive impairment. Sleep deprivation also causes
mental fatigue, decrease in attention span, impairment of long term memory and language
development.

Physical health – Long term disruption of circadian rhythm is associated with a variety of health
issues such as obesity, diabetes, premature mortality, etc. It might negatively influence
conception. The risk of cancer increases in night shift workers, especially breast cancer for women. It also increases the incidence of Mental health – Disruption of circadian system affects cognitive functions and are associated with various diseases that are characterised by altered neurotransmitter signalling. Lack of synchronisation of the various circadian rhythms tend to cause impairments in social communication and increase the risk of psychiatric disorders like autism, schizophrenia, depression, bipolar disorder, etc.

Ways to set back a disturbed circadian clock:
Lifestyle changes like going to bed on time, eating healthy food, regular exercise, taking care of
our mental health, etc. are a few things that can naturally synchronise our sleep wake cycle. A
few ways that can help are listed below:

Exposure to natural light – Seeking out sunlight in the day helps reinforce a disturbed circadian
rhythm. Going outdoors in the morning can be of great help.
Fixed sleep timing – It is always wise to go to sleep and wake up at the same time everyday.
Varying these often does not allow our body clock to align itself.

Regular exercise – Exercise throughout the day makes us tired. Hence, it becomes easy for us to sleep at night.

Avoiding caffeine – These stimulants should be avoided as they put us on alert mode by putting
off our sleep. Hence, it disturbs the natural balance between sleep and wakefulness. People
having difficulty sleeping should definitely avoid caffeine intake.

Naps should be taken for short time durations and early in the afternoon because long duration
naps tend to shift our bedtime, disturbing the natural rhythm.

The light-dark cycle and melatonin are the primary synchronising agents of the circadian
system. Hence, timed exposure to bright light and administration of melatonin have often been
used as treatments of CRSD.

For patients suffering from DPSD, exposure to even a small amount of light in the evening can
be extremely stimulating and can significantly delay their circadian rhythm. It can also suppress the normal release of melatonin. Therefore, avoiding light exposure in the evening must be avoided for them.

Hence, we conclude that the circadian rhythm of our body is vital for us to live a good healthy
life. We must put in a great amount of effort to maintain it. Our children must be aware of its
importance so that they plan their daily routine such that it is not adversely affected. They
should be encouraged to indulge in more outdoor and other extracurricular activities that keep
them away from blue lights of electronic devices, includes a great amount of energy
expenditure that makes them tired and also exposes them to a good amount of sunlight.
Working professionals also need to prioritise their sleep and health. This also requires the
efforts of their organisations and the policy makers. They should make sure not to assign night
shifts to an individual continuously for many days. There should be breaks at regular intervals
so that their circadian rhythm is not severely damaged. Therapy and medications in case of disturbed circadian rhythms should be taken without hesitation. With collective effort we can
ensure a healthy and happy population in our country.

References:

Buhr, E. D., & Takahashi, J. S. (2013). Molecular components of the Mammalian circadian clock. Handbook of experimental pharmacology, (217), 3–27. https://doi.org/10.1007/978-3-642- 25950-0_1

Guo, J. H., Qu, W. M., Chen, S. G., Chen, X. P., Lv, K., Huang, Z. L., & Wu, Y. L. (2014). Keeping the right time in space: importance of circadian clock and sleep for physiology and performance of astronauts. Military Medical Research, 1, 23. https://doi.org/10.1186/2054-9369-1-23

Reddy, S., Reddy, V., & Sharma, S. (2021). Physiology, Circadian Rhythm.[Updated 2020 Jul 10]. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing.

https://www.cdc.gov/niosh/work-hour-training-for-nurses/longhours/mod2/25.html

https://www.sleepfoundation.org/circadian-rhythm

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