Person With a Broken Clock: Disrupted Circadian System

Rishaanko Pyne, Amity University Kolkata

What are Circadian Rhythms?

Circadian rhythms (circa = about; dies = day) are an integral part of eukaryotic life, they are endogenous, inducible biological processes that oscillate over a 24-hour cycle following the circadian environment of the earth. It allows the coordination of biological and behavioral processes with the external temporal environment. Modern industrialized society and the ubiquity of electric lighting have resulted in a fundamental shift in the interaction between an individual’s external environment and endogenous circadian rhythmicity which leads to several psychological and physiological problems to mankind.

Circadian System in Human:

In mammals including humans, the Circadian System consists of the master clock located in the suprachiasmatic nucleus (SCN) in the hypothalamus. This clock is an oscillator that is self-sustaining and controls by neurological, humoral, and other physiological signals, with the help of peripheral clocks present throughout the body and brain. 

The master clock observes the 24-hour light-dark period (the diurnal period) which coordinates the activation of neurotransmitters such as serotonin and norepinephrine. During wakefulness, serotonin and norepinephrine are present at higher levels, while melatonin peaks at night, irrespective of diurnal or nocturnal sleep cycles throughout organisms. SCN also harmonizes with the clock genes found in the peripheral organs and immune cells (e.g., liver, kidney, and heart). Clock genes, such as Clock, Per1, Per2, Bmal1, Cry1, and Cry2, express messenger ribonucleic acids (mRNAs) to generate proteins that, via self-sustaining transcriptional/translational feedback loops, influence circadian processes at the molecular level. 

 The Peripheral circadian clock is a collection of organs inside the body that absorbs external and internal signals to guide the expression of circadian clock genes While the master clock is mostly regulated by the external light / dark cycle, peripheral clocks respond to the autonomic nervous system, body temperature, hormone metabolites, and feed / fast cycles.

Disruption of Circadian System:

Technical effects in industrial life, such as late-night activities, work patterns that require long-term night shifts and shift alterations (i.e. shift work) and jetlag are major environmental disruptors in natural circadian cycles. It is observed that fifteen percent of American workers conduct shift work (Bureau of Labor Statistics 2005), showing the occurrence of circadian disturbance as an abnormal aspect of contemporary life. This transition from the diurnal lifestyle of our ancestors to one that is more prominently nocturnal results in a misalignment between 24-hour day-based natural rhythms and behavioral activity patterns ( i.e. circadian misalignment). Circadian misalignment has a major adverse impact on the cells, tissues, and whole organism’s function. Such modifications can manifest chronic health conditions such as metabolic syndrome, diabetes, cardiovascular disease, cancer, and intestinal disorders.

Besides these other environmental factors, such as alcohol consumption and the timing of food intake, can profoundly affect and disorganize circadian rhythmicity, which is observed on behavioral, cellular, and molecular levels.

Disorders caused due to disrupted circadian rhythm:–

There is plenty of evidence that the circadian system plays a causal role in many disease states, like metabolic diseases and cancer. Disruption of the circadian rhythms, whether they are biological, developmental, or genetically activated can lead to a myriad of physiological and psychological issues. These impacts are encountered daily during transmeridian air travel ( ‘jet lag’) and also by shift workers . The Physiological effects include fatigue, and general ‘malaise’,and also it may sometimes cause gastrointestinal problems and may also lead to decreased immune responses making the individual susceptible to several diseases. Besides this, it may also cause obesity, diabetes, cardiovascular, and intestinal disorders and may sometime also lead to cancer.  It also causes psychological problems which can manifest decreased concentration, depression, and poor remembering capability in individuals. In some cases disrupted circadian system and lack of sleep also leads to severe neurological disorders.

Conclusion:

The purpose of this article was to present the recent results in research to investigate how the circadian timing mechanism can influence our health. It is clear that interruption of the circadian clock, at any or all stage of physiology, potentially affects the health of our body. This is because our brains and bodies have not been able to adjust properly to the rapid changes in our lifestyles that have occurred over the past 100 years. A more clear understanding of these changes, and the factors that lead them to fail, could provide for interventions to mitigate, or even perhaps reverse, the effects of circadian disruption on mental and physical health.

Also read: SADS-CoV, a new type of coronavirus can infect humans

References:

1. Karatsoreos IN. Effects of circadian disruption on mental and physical health. Curr Neurol Neurosci Rep. 2012 Apr;12(2):218-25. doi:http://10.1007/s11910-012-0252-0 . PMID: 22322663.
2. Matenchuk BA, Mandhane PJ, Kozyrskyj AL. Sleep, circadian rhythm, and gut microbiota. Sleep Medicine Reviews. 2020 Oct;53:101340. DOI: http://10.1016/j.smrv.2020.101340. 
3. Voigt RM, Forsyth CB, Keshavarzian A. Circadian disruption: potential implications in inflammatory and metabolic diseases associated with alcohol. Alcohol Res. 2013;35(1):87-96. PMID: 24313168; PMCID: PMC3860420.
4. Walker, William & Walton, James & Devries, A & Nelson, Randy. (2020). Circadian rhythm disruption and mental health. Translational Psychiatry. 10. http://10.1038/s41398-020-0694-0

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