What is Circadian Rhythm?

What is Circadian Rhythm?

The term ‘circadian’ has been derived from the Latin phrase circa (approximately) and diem (day), indicating a roughly 24-hour cycle. ‘Rhythm’, or rhythmicity, is an essential property of all living organisms, from single cells to complex animals.

Circadian rhythms enable periodic changes in organisms, enabling them to adapt and thrive by optimizing their usage of environmental resources — thus putting them at a selective advantage in evolutionary terms. Circadian rhythms dictate flowers opening and closing at precise times, and nocturnal animals avoiding predators during the day by staying within their shelters. These rhythms synchronize internal and external environments, which is crucial for organisms’ survival.

Circadian Rhythm Definition

According to the National Cancer Institute, a circadian rhythm is "the natural cycle of physical, behavioral, and mental changes that the body goes through in a 24-hour cycle." Influenced by light and darkness, these rhythms, also known as the body's clock, affect sleep, appetite, hormones, and body temperature.

Chronobiology

Chronobiology is a sub-discipline of biology that deals with the mechanisms underlying biological timekeeping systems and the consequences when disrupted. Various biological cycles observed are high-frequency cycles (hormonal secretions during the day), monthly and annual cycles (reproductive cycles), and daily cycles (sleep-wake cycle).

Characteristic Features of Circadian Rhythms

To be considered a circadian rhythm, several features must be present:

1.  Self-sustained nature: Observed by French scientist De Mairan, circadian rhythms persist regardless of external cues, indicating an internal timekeeping mechanism.

2.  24-hour cycle: These rhythms last approximately 24 hours, allowing the internal biological clock to align continuously with the light-dark cycle.

3.  Entrainment: Circadian rhythms can align with environmental changes, resetting when external factors shift.

4.  Ubiquitous nature: Present in all organisms, these rhythms exhibit similar properties and responses to external cues.

5.  Cellular origin: Circadian rhythms are generated at the cellular level, seen in both unicellular organisms and complex mammals.

Diurnal Rhythms and Circadian Rhythms

Not all 24-hour biological cycles are circadian rhythms. Some cycles are exogenously driven and disappear when the environment is constant, whereas circadian rhythms persist under ongoing exogeneous conditions.

The Master Clock

In humans, almost all physiological aspects, from cerebral activity to renal function, exhibit rhythmicity. Notably, these rhythms persist under constant conditions despite not receiving any environmental cues – driven by an endogenous circadian timing system. The master clock in mammals is located in the brain's suprachiasmatic nuclei (SCN) within the anterior hypothalamus. This clock, sensitive to light, receives input directly through the eyes, particularly from specialized ganglion cells in the retina containing melanopsin.

Different cells communicate with each other to communicate to synchronize electrical signals, influencing endocrine glands and periodic hormone release. The SCN relays information to the pineal gland, regulating melatonin secretion, which peaks at night. Cortisol, another hormone, peaks during the day to promote alertness. Other hormones like vasopressin, leptin, insulin, and acetylcholine also play roles in circadian rhythms, with receptors spread throughout the body, synchronizing peripheral clocks of various organs.

In short, the information relayed by the eyes travels to the master clock in the brain, and through that, the various clocks in the body are synchronized. In this manner, the biological clock controls body temperature, sleep-wake cycle, appetite, and thirst. Body temperature drops while sleeping and rises during awake hours. Similarly, the rate of metabolism keeps on changing throughout the day. External cues such as exercise, temperature, and social activity can influence the internal clock, but light remains the most potent.

Genetics

At least half of all the genes in the genome oscillate with circadian rhythms. The Period and Cryptochrome genes are among the most critical genes responsible for this process. These genes are activated by the CLOCK and BMAL1 transcription factors. CLOCK and BMAL1 initiate the transcription of their target genes, forming large protein complexes with additional polypeptides. Once these complexes reach a specific concentration, they inhibit the activity of CLOCK and BMAL1, stopping further protein formation. When the repressor complexes diminish, CLOCK and BMAL1 activity resumes, starting a new cycle.

These genes encode proteins that accumulate in the cell's nucleus overnight and decrease during the day, influencing alertness, sleepiness, and wakefulness. Environmental factors, such as light exposure, can also reset the Period and Cryptochrome genes.

The expression of Period genes can be stimulated by various early transcription factors, including cyclic AMP response element-binding protein, serum response factor, glucocorticoid receptor, and heat shock transcription factor 1. The modulation of Period genes by systemic cues, neurotransmitters, hormones, temperature, and second messengers plays a crucial role in synchronizing circadian clocks and linking different body rhythms.

Circadian Rhythms across the Lifespan

Infants and Toddlers:

In utero, a fetus's SCN oscillates in sync with maternal cues, but this synchronization is lost at birth. Newborns lack a circadian rhythm, leading to erratic sleep-wake patterns. By about two months, babies start releasing cortisol, and by three months, they begin producing melatonin. As their body functions mature and they develop a circadian rhythm, toddlers establish a more regular sleep schedule.

Teenagers:

Teenagers often experience a sleep-wake phase delay, making them feel tired later at night and causing difficulty waking up early. This shift is partly driven by sex hormones. Teenagers need 9 to 10 hours of sleep but often face chronic sleep deprivation due to late sleep onset and early school start times.

Adults:

Adults with healthy habits typically have a regular circadian rhythm and sleep for 7 to 9 hours. They are most tired between 2 to 4 am and 1 to 3 pm. "Eveningness" peaks in the late teens or early twenties. As people age, their circadian rhythms shift toward "morningness," causing them to go to bed and wake up earlier. This change can be due to reduced light exposure, as older adults spend more time indoors.

Effect of Circadian Rhythms on the Body

Circadian rhythms significantly impact almost all body systems, making their maintenance crucial for health. Disruptions in circadian rhythms can have both short-term and long-term health effects.

Short-term effects:

1. Memory loss
2. Delayed wound healing
3. Digestive problems
4. Lack of energy
5. Hormonal changes affecting fertility and body temperature

Long-term effects:

1. Cardiovascular Disease: Increased resistin levels (an atherosclerosis biomarker) and elevated triglyceride levels, associated with plaque buildup in arteries, cardiovascular diseases, and stroke.
2. Metabolic Disorders: Eating during the resting period can lead to increased body mass, altered metabolic gene expression, higher body mass index, and diabetes. Circadian rhythms regulate blood sugar and cholesterol.
3. Mental Health: Circadian health influences the risk of psychiatric illnesses like depression and bipolar disorder, as well as neurodegenerative diseases such as dementia.
4. Immune System and Cancer: Circadian rhythms impact the immune system and DNA repair processes, potentially affecting cancer prevention and treatment effectiveness.
5. Drug Efficacy: Understanding circadian rhythms can enhance drug efficacy and tolerability, as shown in studies on glucocorticoid chronotherapy for rheumatoid arthritis.
6. Sleep Patterns: The SCN synthesizes melatonin to regulate sleep. A stable sleep cycle enhances daytime productivity. Disrupted sleep-wake cycles can lead to difficulty falling asleep, fragmented sleep, and reduced total sleep time. Disturbed circadian rhythms may also contribute to obstructive sleep apnea, a disorder causing non-restorative sleep.

Factors that influence Circadian Rhythms

Genetic Mutations: Mutations in genes responsible for circadian rhythm, such as the Period and Cytochrome genes, can disturb these rhythms.

Jet Lag Disorder: Traveling across multiple time zones disrupts the sleep-wake cycle. The biological clock takes time to realign with the new time zone, causing fatigue and sleep disturbances until it adjusts.

Shift Work Disorder: Working night shifts and sleeping during the day puts the sleep-wake cycle at odds with natural daylight hours. This disruption can lead to cardiovascular diseases, malignancies, and metabolic syndrome over time.

Seasonal Affective Disorder (SAD): SAD affects people in countries with low light exposure during winter, leading to depression. The human body struggles to synchronize its clock with low-intensity morning light during winter.

Non-24-Hour Sleep-Wake Disorder: Common in blind individuals, this disorder arises from the lack of light-based cues that drive circadian rhythms. Their body clock shifts forward or backward each day, depending on whether their endogenous period is shorter or longer than 24 hours.

Indoor Lighting and Electronic Devices: Blue light from electronic devices suppresses melatonin production five times more than orange-yellow light, disrupting sleep.

Besides these factors, medications, stress, poor sleep habits, and irregular work hours can clash with the internal clock, leading to sleep disorders and chronic health conditions such as diabetes, depression, obesity, and bipolar disorder.

How to Maintain a Healthy Circadian Rhythm

Adopting healthy habits can help maintain a stable circadian rhythm.

1. Sun Exposure: Natural sunlight reinforces circadian cues.
2. Consistent Sleep Schedule: Maintain a regular bedtime and wake-up time.
3. Short Naps: Keep naps short and preferably early in the afternoon.
4. Daily Exercise: Exercise supports the internal clock and aids in sleep.
5. Avoid Stimulants: Avoid caffeine, alcohol, and nicotine, especially in the afternoon.
6. Bedroom Ambiance: Create a comfortable sleep environment with proper lighting and temperature.
7. Power Down Electronic Devices: As stated earlier, artificial light interferes with circadian rhythm. Turn off all devices at least 90 minutes before sleep. Engage in relaxing activities like reading or meditation. Use night lights or lamps instead of overhead lights.
8. Auditory Stimulation: Use brain entrainment techniques to improve sleep quality. Professional and scientific sound combinations can cause sleep by tuning our brainwaves into specific frequencies like deep sleep delta waves. Brainwave entrainment has also been used to treat insomnia and induce sleep. However, it’s not as simple as simply listening to any sound wave. For brainwave synchronization, a specific combination of sound waves corresponding to a particular frequency's rhythm must be heard.

Bottom Line

Circadian rhythms are crucial for overall well-being, helping maintain a healthy sleep-wake schedule. Disruptions can lead to various health issues, but adopting an active, healthy lifestyle with adequate rest can help maintain these rhythms. If experiencing prolonged sleep difficulties or extreme daytime fatigue, try implementing the healthy habits mentioned.

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