Circadian Rhythm: Nature’s Intelligent clock cycle

• Embedded deep within the brain is a master clock, Suprachiasmatic Nucleus (SCN Weaver, 1998) inside the hypothalamus that regulates the timing of many of the biological, hormonal, and behavioral processes that occur in the human body, playing a critical role in sleep, metabolism, aging and overall health and maintaining homeostatic .
• Circadian Rhythms (CRs) are biological temporal processes that display endogenous, entrainable free-running periods that last approximately 24 h. They are driven by molecular internal clocks which can be reset by environmental light-dark cycles on a feedback loop (Edery, 2000).
• Researchers have shown over the past few years that cellular and regional, peripheral clocks can be found in the liver, kidneys, pancreas, heart, fat and other organs and tissues that are synchronized with the sleep-wake cycle (Zylka et al., 1998). These cellular clocks regulate the activity of 3 to 10 percent (and up to 50 percent) of genes in various tissues and other parts of the body as well, by regulating the expression of clock-controlled genes (Ccg).
• The first clock gene was isolated, or cloned, from fruit flies in 1984. Now, we have identified dozens of genes in cyanobacteria, plants, and mammals (Reppert and Weaver, 2002) that help the body keep time, including those going by such names as Clock, Per (for period) and Tim (for timeless).
• Important genes are involved in CRs including Clock (Circadian locomotor output cycles kaput), Bmal1 (brain and muscle aryl-hydrocarbon receptor nuclear translocator-like 1), Cry1 (cryptochrome 1), Cry2 (cryptochrome 2), Per1 (Period 1), Per2 (Period 2), Per3 (Period 3), and Ccg. They organize transcription/translation autoregulatory feedback loops comprising both activating and inhibiting pathways (Reppert and Weaver, 2002; Schibler and Sassone-Corsi, 2002) forming a complex network.
• In mammals, sleep-awake and feeding patterns, hormone secretion, heart rate, blood pressure, energy metabolism, and body temperature exhibit CRs.
• Zeitgebers like light and food (rhythmically occurring phenomena that have primary control over circadian rhythm) for e.g. Routinely eating or sleeping at the wrong times may throw these peripheral clocks out of sync with the master clock in the brain, seen often in people with shift working, frequent trans meridian air flight, exposure to artificial light.
• There is sufficient evidence to suggest that these chronobiological disruptions predispose individuals to the development of obesity, diabetes, cardiovascular diseases, sympathetic/parasympathetic dysfunction, hypertension, ailments of the heart and stomach, as well as various cancers, neurological and neurodegenerative diseases, and psychiatric illnesses including depression and other disorders.
• Resynchronizing the body’s many clocks may help to restore health and proper functioning and prevention of Many chronic illnesses.
• In the presence of light, particularly of blue wavelengths, the hormone melanopsin is produced, inhibiting the release of melatonin. at night, in the absence of light and melanopsin, melatonin is released and contributes to sleep onset.
• During the light period, particularly in the morning, larger amounts of cortisol and insulin are released. Notably, insulin secretion and insulin sensitivity are both controlled by circadian rhythms. Insulin production diminishes and remains low throughout the day unless foods requiring insulin are consumed. During the morning, we are particularly sensitive to the action of insulin. as the day progresses, we become more resistant to insulin, and during sleep we are most insulin resistant.
• Disruption in the circadian function leads to abnormal levels of insulin, leptin, and ghrelin, hormones affecting appetite, satiety, metabolic rate, and fat storage—a key hormone mitigating this function is melatonin.
• Night shift workers have among the highest rates of obesity due to the presence of light at night and disordered sleep and eating rhythms.
• Circadian disruptors related to the second zeitgeber, food, include frequent snacking, high-fat foods, late-night eating, and medications that alter sleep-wake patterns. These disruptions lead to altered melatonin production, a potent hormone that, when dysregulated, leads to insulin resistance, glucose insensitivity, and sleep disturbance. Interestingly, because food is also a driver of the circadian clock, intermittent fasting mitigates circadian dysfunction and, if performed appropriately, resets a dysregulated circadian clock.
• CR dysfunctions in blood pressure and heart rate, are involved in arrhythmias which may lead to sudden cardiac death, myocardial infarction or stroke, often occurring at the early morning during the surge in blood pressure.
• CRs are dissipative structures due to a negative feedback produced by a protein on the expression of its own gene (Goodwin, 1965; Hardin et al., 1990). They operate far-from- equilibrium and generate order spontaneously by exchanging energy with their external environment (Prigogine et al., 1974; Goldbeter, 2002; Lecarpentier et al., 2010).