The central neuro-anatomic structure responsible for both generation and synchronization of 24-hour circadian rhythms are self-sustaining and persist even in the absence of time cues with proper precision. The period, phase or the amplitude of oscillation and sensitivity to synchronization with the various systems represent circadian rhythm. Circadian oscillations are generated by time-keeping clock genes and influenced by the entrainment of the circadian system by the environmental and behavioral aspects of the subjects.
This article explores the circadian rhythm, how it works in different systems of the body, the coordination of circadian rhythm and sleep, factors that influence the circadian systems and some tips for the maintenance of circadian rhythm.1
Circadian rhythm in humans:
What is a circadian rhythm?
Circadian rhythms are ubiquitous biological mechanisms of a 24-hour period that are commonly observed in every species from cyanobacteria to humans. It arises from innate and genetically organized system known as biological clock. These time-keeping systems of the body allows organisms to prepare and anticipate for the changes in the physical and environmental conditions to maintain and behave appropriately.2 The word circadian is derived from the latin words circa meaning around and diēm meaning day like around the day or diurnal variations. Circadian rhythms are periodic mechanisms that are generated endogenously by themselves every 24-hour even in the absence of time cues.3
Characteristics of circadian rhythm4
Circadian rhythms coordinate the physical and mental system in the body throughout the day. A circadian rhythm is characterized by following features:
- Self-sustaining physiological functions of the body
- Persistent in the presence or absence of dark-light cycles
- Ability to synchronize or entrain with the changes in routine or external environment
- Ubiquitous in nature i.e. observed in wide range of species and maintain several systems of the body
- Generated from the cellular levels
Anatomical organization of internal clock
In humans, circadian rhythms originate from the cluster of nerve cells called suprachiasmatic nucleus (SCN) in the anterior hypothalamus at the base of skull. SCN’s plays the role of master pacemaker, which regulates the various rhythmic systems in the body. The postulated mechanism by which brain talks to the body is the signals emitted by SCN acting on other nerves (neural signals) distributed by blood i.e. neurohormonal pathways.4
Difference in circadian rhythm and biological clock:
Circadian rhythms are daily cycles that regulate the physical, mental and behavioral changes in humans. On the other hand, biological clocks are the innate time-keeping mechanisms of the body. They are composed of specific protein molecules throughout the body that produce circadian rhythm and regulate the timing of the circadian variations. A circadian rhythm is an effect of the function of biological clock, but not all biological clocks are circadian.2
Factors disrupting the circadian rhythm:
Diurnal variations in various physiological systems are not only driven by the endogenous circadian rhythm, but also by the environmental and behavioral factors that includes light, dark, sleep, food intake and physical activity. The misalignment of the circadian rhythm can be induced by several external factors:
Insufficient day light exposure: Light is considered as the primary factor for the maintenance of the 24-hour centered clock. Bright light exposure during the day-time is associated with production of melatonin at night and insufficient exposure during the day may misalign the circadian rhythm and consequently impair the physiological mechanism.3 Studies have proved that exposure to sufficient light during the day helps regulating the carbohydrate metabolism and reduced insulin requirement in diabetes which in turn helps in improving the glycaemic control.5 In overweight individuals, morning exposures can help in balancing the leptin and ghrelin levels that can further help in improving the quantity and quality of sleep.6
Exposure to light at night: In addition to the insufficient exposure to daylight, prolonged exposure to artificial light in the evening or at night is also associated with misalignment in the circadian rhythm.3 Studies have reported that exposure to bright light at night increases the insulin resistance and glucose levels of blood in comparison to dim light exposure.7 Another randomized controlled trial reported that light exposure at night disrupts the circadian rhythm of carbohydrate metabolism and increases post- prandial glucose levels.8
Shift workers: In shift workers due to the restricted sleep during the night, it is difficult to adapt to the day sleeping and this could cause misalignment of the circadian rhythm. Decreased quantity of sleep during day leads to chronic sleep loss and causes detrimental effects on cognitive functions like alertness, vigilance, psychomotor skills, mood and overall performance.1
Sleep timing, deprivation and disorders: Circadian misalignment can be induced by the phase shift in the timing of the sleep. Studies have reported that in night shift workers a mistimed sleep during the day can impair the glucose metabolism and lipid levels. This could lead to decreased quality of sleep and weight gain. In chronic sleep disorders, inability to sleep during the day leads to misalignment of circadian rhythm. In primary sleep disorders such as narcolepsy and sleep apnea, sleep deprivation happens due to difficulty in breathing that can disrupt the sleep patterns. This could lead to tiredness and disorientation on the next day.1
Circadian rhythm and sleep
In humans, circadian rhythm influences many aspects of physiological and behavioral functions. The sleep/wake cycle is perhaps the most accepted manifestation of the circadian rhythm. The output of circadian pacemaker activity can be easily reflected by the timing of the sleep/wake cycle. Sleep is an independent biological mechanism needed for every animal and without proper sleep it is difficult to sustain life. Sleep is dependent on circadian rhythm as well as the satiety homeostasis. Acute sleep loss, interrupted sleep patterns or chronic sleep disorders can increase the drive for sleep and impair the behavioral performance.
During the day, light exposure send signals to the circadian pacemaker to generate alertness and helps in keeping awake and active. The output of circadian rhythm is reflected by the daily variation of alertness and neuro-behavioral performance in humans. Sleepiness, vigilance, short-term memory, ability to concentrate are mostly impaired in the absence of circadian rhythm. During the 24-hour entrainment, the circadian pacemaker opposes the increased drive for sleepiness in the later half of the day by sending signals to SCN to maintain waking. A few hours before the bed-time, pineal gland releases the sleep promoting melatonin into the blood stream. Melatonin does not disturb 24-hour oscillation of SCN instead, it serves to quiet the waking signals emitted by SCN, and helps promoting the sleep.1
Circadian rhythm in various physiological systems:
Circadian rhythm and metabolism: the circadian system regulates the metabolism, physiology and behavior in a daily cycle of circadian rhythm. The circadian rhythm consists of two parts, a central control SCN and peripheral clocks located in other body tissues such as liver, pancreas, gastrointestinal tract, skeletal muscles and adipose tissues. Circadian control with peripheral neurohormonal system modulates a wide range of targets such as glucocorticoids, fatty acids, carbohydrates and cholesterol. The central clock in SCN regulate the metabolic activities through cortisol and melatonin particularly. The peripheral tissues integrate these autonomic signals with environment and behavioral factors like light, dark, sleep, activity, feeding and regulate metabolism in a rhythmic fashion. Several studies have suggested that the disruption of circadian rhythm in metabolism can lead to increase in risk of metabolic disease.3 Patton DF and Mistlberger RE. (2013) studied the mechanisms that relate the circadian rhythm and the periodic environmental or physiological stimuli such as meal timing. It was observed that the rhythm of daily food intake provokes stimuli that entrains the central and peripheral systems to act according to the timing of the food intake.9
Circadian rhythm and autonomic nervous system: The circadian rhythm is controlled by the autonomic signals from the suprachiasmatic nucleus in the anterior hypothalamus. It acts as a pacemaker and synchronizes the autonomic and peripheral outputs with the circadian system. It collects information from the environment, body and optimizes the autonomic, hormonal and functional responses. It puts a time stamp on every mechanism in the body and organizes various functions. This theory gives an idea that most of modern day diseases like diabetes, hypertension, obesity are induced by the internal desynchronization of the rhythmic processes of the central and peripheral systems.10
Circadian rhythm and cardiovascular system: The daily activities at different times of the day of various physiological parameters of cardiovascular system are maintained by the diurnal variations or circadian rhythms. Studies have postulated that almost all the cardiovascular events exhibit a circadian rhythm. It shows higher frequencies in the morning after waking up, in upright posture and during activities but relatively lower during the sleep. It has been implicated that both endogenous factors such as circadian variability in autonomic function, blood catecholamine concentrations, coagulability, accelerated response to morning nor-epinephrine and exogenous factors like rest, activity, stress and posture change influence the cardiovascular events in the body.11
Circadian rhythm and immune system: In blood, the key parameters of immune system show circadian rhythms such as the number of circulating homopoietic stem cells, hormones as well as the cytokines. The parameters oscillate around the circadian rhythm according to the rest-activity phases. The homopoietic stem cells and most of the leukocytes peak during the resting phases i.e. during the night. On the other hand, levels of glucocorticoids, adrenaline, noradrenaline and proinflammatory cytokines show peak concentrations during the active phases i.e. around the daytime. The oscillations of the immune components with the dark-light phases suggest that the rhythmic changes of the factors have the potential to affect tissues, and can increase the risk of disease onset along with modulating therapy.12
Circadian rhythm and body temperature: The homeostatic control of the body temperature helps in ensuring stability and preventing deviation from the ideal set point. The circadian control of body temperature helps in stabilization of oscillation in body temperature around the active and rest phases. It has been postulated that circadian pacemaker acts on the thermoregulatory thermostat to keep it set by elevating temperature during the day and lowering it during the night. It has been observed that autonomic heat loss during the low body temperature and heat conservation during the high body temperature are activated during the circadian phases of thermoregulation. To simplify, circadian rhythms helps to compensate for the temperature variations due to the external and internal environment.13
Circadian rhythm and hormonal changes: Suprachiasmatic nucleus in higher centers along with peripheral systems controls the circadian peak of hormones in blood concentration throughout the day. Several hormones are proven to have daily oscillations and the most researched ones are melatonin, cortisol, gonadal steroids, prolactin, thyroid hormones and growth hormone. The metabolic hormones such as insulin, leptin and ghrelin also oscillate around the day and night activity and follow a circadian system. Melatonin is secreted from the pineal gland which directly correlates with day length. Its peak is reached around the middle of the night, which inputs the SCN to decrease the waking signals and facilitate sleep.14
Tips for balancing the circadian rhythm
It is not possible to completely control the circadian rhythm, but opting some healthy choices can help with maintaining the biological clock and circadian rhythm reducing the risk for the development of several health disorders.
Get some sun: As discussed above, light exposure during the day is very important for the night release of melatonin that helps in sleep onset and better quality of sleep.3
Follow a sleep schedule: sleep timing is a very important factor in maintaining a healthy circadian system. Sleeping around the same time everyday entrains the body’s circadian rhythm to induce better and quality sleep.
Workout: Some daily activity helps to set the rhythm and make it easier to fall asleep at night and improves the quality of sleep.15
Sleeping in dim light and ambient temperature: As discussed above, exposure to bright light at night leads to disruption of the circadian rhythm. Sleeping in dim light with ambient temperature helps to facilitate the sleep onset by lowering the core temperature of the body and improves the quality of sleep.16
Short afternoon naps: long or late evening naps can hinder with the night-time sleep and such habits can disrupt the circadian rhythm of the body. Short post-lunch nap helps in gaining the energy and refreshes the mind.17
Human beings and other organisms have endogenous physiologic systems that are timed rhythmically to synchronize enzyme, hormone, metabolism and energy levels with organ activity. To conclude, these biological rhythms are self sustaining oscillations that have a specific set of characteristics like period, amplitude and phasing. The biological rhythms repeating in a given period of 24-hour are known as circadian rhythms. Circadian rhythms play a central role in the management of various physiological mechanisms in body and misalignment of these rhythms can lead to increased risk of several metabolic, cardiovascular and sleep disorders. Hence, future research is required to completely understand the interrelations, effects of alignments and therapeutics to treat the circadian misalignments.
- Czeisler CA, Gooley JJ. Sleep and circadian rhythms in humans. Cold Spring Harb Symp Quant Biol. 2007; 72:579-597. doi:10.1101/sqb.2007.72.064
- Chung S, Son GH, Kim K. Circadian rhythm of adrenal glucocorticoid: its regulation and clinical implications. Biochim Biophys Acta. 2011;1812(5):581-591. doi:10.1016/j.bbadis.2011.02.003
- Poggiogalle E, Jamshed H, Peterson CM. Circadian regulation of glucose, lipid, and energy metabolism in humans. Metabolism. 2018; 84:11-27. doi:10.1016/j.metabol.2017.11.017
- Vitaterna MH, Takahashi JS, Turek FW. Overview of circadian rhythms. Alcohol Res Health. 2001;25(2):85-93. https://pubmed.ncbi.nlm.nih.gov/11584554/
- Sone Y, Hyun KJ, Nishimura S, Lee YA, Tokura H. Effects of dim or bright-light exposure during the daytime on human gastrointestinal activity. Chronobiol Int. 2003;20(1):123-133. doi:10.1081/cbi-120017688
- Figueiro MG, Plitnick B, Rea MS. Light modulates leptin and ghrelin in sleep-restricted adults. Int J Endocrinol. 2012; 2012:530726. doi:10.1155/2012/530726
- Albreiki MS, Middleton B, Hampton SM. A single night light exposure acutely alters hormonal and metabolic responses in healthy participants. Endocr Connect. 2017;6(2):100-110. doi:10.1530/EC-16-0097
- Hirota N, Sone Y, Tokura H. Effect of evening exposure to dim or bright light on the digestion of carbohydrate in the supper meal. Chronobiol Int. 2003;20(5):853-862. doi:10.1081/cbi-120024216
- Patton DF, Mistlberger RE. Circadian adaptations to meal timing: neuroendocrine mechanisms. Front Neurosci. 2013; 7:185., doi:10.3389/fnins.2013.00185
- Buijs RM, Escobar C, Swaab DF. The circadian system and the balance of the autonomic nervous system. Handb Clin Neurol. 2013; 117:173-191. doi:10.1016/B978-0-444-53491-0.00015-8
- Guo YF, Stein PK. Circadian rhythm in the cardiovascular system: chronocardiology. Am Heart J. 2003;145(5):779-786. doi:10.1016/S00028703(02)94797-6
- Scheiermann C, Kunisaki Y, Frenette PS. Circadian control of the immune system. Nat Rev Immunol. 2013;13(3):190-198. doi:10.1038/nri3386
- Refinetti R. The circadian rhythm of body temperature. Front Biosci (Landmark Ed). 2010; 15:564-594. doi:10.2741/3634
- Gnocchi D, Bruscalupi G. Circadian Rhythms and Hormonal Homeostasis: Pathophysiological Implications. Biology (Basel). 2017;6(1):10. doi:10.3390/biology6010010
- Glavin EE, Ceneus M, Chanowitz M, et al. Relationships between sleep, exercise timing, and chronotype in young adults. J Health Psychol. 2020;1359105320926530. doi:10.1177/1359105320926530
- Zhang N, Cao B, Zhu Y, Indoor environment and sleep quality: A research based on online survey and field study. Environ. 2018; 137: 198-207. doi:10.1016/j.buildenv.2018.04.007.
- Milner CE, Cote KA. Benefits of napping in healthy adults: impact of nap length, time of day, age, and experience with napping. J Sleep Res. 2009;18(2):272-281. doi:10.1111/j.1365-2869.2008.00718.x