Chester Wu, MD. Definition How It Affects Health Jump to More Topics. Next up video playing in 10 seconds. Research suggests that circadian rhythm disruption and misalignment may play a role in the development or progression of the following health issues: Diabetes Heart disease Some cancers Depression.

But other factors can disrupt circadian rhythms, too. This is especially important in the two hours before going to bed, Wright says. Reduce exposure to artificial light at night. In particular, try to minimize time spent in harsh, bright lighting like that from fluorescent bulbs or the blue light from your cellphone or computer.

Use lamps with soft lighting in your home, and if you need to use your devices, shift them to a setting where blue light is muted.

Get outside in the morning. Or expose yourself to plenty of other bright light in the morning. Natural light via sunlight is ideal, but artificial light is better than none.

If you work indoors, Wright recommends trying to set up your desk near a window, if possible. If not, he suggests taking your morning coffee outdoors first to get some morning sun exposure. Ask your doctor about melatonin supplements. Melatonin is a naturally occurring hormone produced by the body to help promote sleep at night.

In some cases, such as before or after traveling across time zones or for short-term bouts of insomnia, low doses of melatonin supplements 1 to 3 milligrams can help the body readjust to a healthy sleep-wake schedule, according to Johns Hopkins Medicine.

Editorial Sources and Fact-Checking. Resources Ma MA, Morrison EH. Neuroanatomy, Nucleus Suprachiasmatic. January Carskadon MA, Acebo C, Jenni OG. Regulation of Adolescent Sleep: Implications for Behavior. Annals of the New York Academy of Sciences.

January 12, Gale JE, Cox HI, Qian J. Disruption of Circadian Rhythms Accelerates Development of Diabetes Through Pancreatic Beta-Cell Loss and Dysfunction.

Journal of Biological Rhythms. October 1, Knutsson A, Boggild H. Shiftwork and Cardiovascular Disease: Review of Disease Mechanisms. Reviews on Environmental Health. Savvidis C, Koutsilieris M.

Circadian Rhythm Disruption in Cancer Biology. Molecular Medicine. September Germain A, Kupfer DJ. Circadian Rhythm Disturbances in Depression. Human Psychopharmacology. October Urrestarazu E, Iriarte J.

Nature and Science of Sleep. January 14, Okawa M, Nanami T, Wada S, et al. Four Congenitally Blind Children With Circadian Sleep-Wake Rhythm Disorder. March Christopher D, Melanson EL, McHill AW, Wright KP. Mistimed Food Intake and Sleep Alters Hour Time-of-Day Patterns of the Human Plasma Proteome.

Biological Sciences. May 21, Skene D, Skornyakov E, Chowdhury NR, et al. Separation of Circadian- and Behavior-Driven Metabolite Rhythms in Humans Provides a Window on Peripheral Oscillators and Metabolism. Proceedings of the National Academy of Sciences of the United States of America.

July 24, Reeth O, Sturis J, Byrne MM, et al. Nocturnal Exercise Phase Delays Circadian Rhythms of Melatonin and Thyrotropin Secretion in Normal Men. American Journal of Physiology: Endocrinology and Metabolism. June 1, Circadian Rhythms and Circadian Clock. National Institute for Occupational Safety and Health.

April 1, Circadian Rhythms. National Institute of General Medical Sciences. May 4, Circadian Rhythm Sleep Disorders. In an experimental study, circadian rhythm disorder caused cardiovascular and renal damage in hamsters [ 14 ].

In a study conducted with schizophrenic patients, participants had severe circadian sleep-wake disorders although their mood, mental status, and psychotic episodes were stable [ 15 ].

In this review, the role of circadian rhythm in metabolic processes and the bidirectional effects of circadian rhythm on energy balance were examined. In accordance with this purpose, studies which were published from to were reviewed. In addition, 3 significant articles which were published in , , and were also added.

Basically, Google Academic bibliographic database , PubMed, Scopus, Web of Science, and Science Direct databases were used to scan scientific articles. Besides, resources in Gazi University Central Library were also scanned. At the end of this scanning, 4, articles were found.

After screening titles and abstracts, duplicate articles and articles that were not published in English were excluded. The final count of articles was 82, which consisted of articles that were free and available in the form of full text.

In addition, the book chapters were also used to examine the subject. Many studies explain the relationship between human physiology, certain diseases, and circadian rhythm [ ].

Metabolic homeostasis is an essential component that regulates energy metabolism, especially in adipose tissue. The adipose tissue is a central metabolic organ that regulates the whole-body energy homeostasis.

The white adipose tissue functions as a key energy reservoir for other organs, whereas the brown adipose tissue accumulates lipids for cold-induced adaptive thermogenesis.

Adipose tissues secrete various hormones, cytokines, and metabolites termed as adipokines that control systemic energy balance by regulating appetitive signals from the central nervous system as well as the metabolic activity in peripheral tissues [ 16 ].

For example, leptin has specific receptors on the hypothalamus and is released from the main adipocytes. This hormone plays a regulatory role in energy metabolism by increasing the activation of the sympathetic nervous system and increasing thermogenesis by increasing thyroid hormones.

In thermogenesis, UCP uncoupling protein inhibits ATP synthesis in mitochondria, allowing energy to be consumed as heat. Leptin increases the level of thyroid hormones and activation of the sympathetic central nervous system, resulting in more UCP formation and thus greater energy use [ 17 ].

The release of leptin hormone occurs in a circadian cycle and serum leptin levels peak at night [ 18 ]. Thus, disruption of circadian balance can affect leptin secretion, thermogenesis, and energy homeostasis, indirectly. On the contrary, some hormones released from the hypothalamus show more activity at night.

If the crosstalk between circadian rhythm and growth hormone is disrupted via sleep disorders, growth hormone cannot be released at normal levels. Therefore, it is necessary to pay particular attention to the sleep patterns of children [ 19 ]. Cortisol is a steroidal hormone secreted from the adrenal glands.

It regulates many metabolic processes such as glycogenolysis, lipolysis, and proteolysis [ 20 ]. The amount and frequency of cortisol secretion is regulated via the circadian rhythm. The cortisol concentration in circulation reaches a peak level just before waking in the morning.

The cortisol gradually declines throughout the day. It reaches its lowest level during sleep after midnight [ 21 ]. Cortisol is a major hormone that regulates the metabolic events in the body.

It increases the use of cortisol, glucose, free fatty acids, and amino acids from endogenous fuel stores. Therefore, high levels of cortisol function as a catabolic hormone that reduces lean body and muscle mass, and increases energy consumption [ 22 ].

In addition, glucose tolerance and insulin secretion vary throughout the day. In the natural course of metabolism, both insulin sensitivity and insulin secretion decrease at night especially between and a.

in comparison to morning hours. This metabolic process, the dawn phenomenon, highlights the impact of circadian control on glucose metabolism [ 23 ].

In the natural physiological processes of the body, hormones working as antagonists of insulin especially growth hormone exhibit hyperinsulinemic activity because of the decrease in insulin secretion between and a. This is counteracted with additional physiologic insulin secretion in non-diabetic or non-insulin-dependent individuals.

Conversely, when insulin release is disturbed, the effect of growth hormone released during the night, especially in diabetic patients, may not be mitigated.

This results in a pathologic circadian rhythm, which can lead to morning hyperglycemia independent of eating patterns [ 24 ]. Melatonin is an important hormone in circadian synchronization.

This hormone is involved in many biological and physiological regulations in the body. It is an effective hormone for human biorhythm circadian rhythm. The main role of this hormone is to maintain the biological clock and to adjust the body rhythm [ 25 ].

Synthesis and release of melatonin is stimulated in the dark, at night, while it is suppressed by light during the day [ 1 ].

Especially between p. and a. However, exposure to light at night causes the plasma melatonin levels to fall [ 1 ]. Lipid metabolism is also affected by circadian oscillations. Studies show that many proteins related to lipid metabolism e. In addition, mice studies show that cholesterol and lipid absorption in the dark phase are higher than in the light phase [ 28 ].

Some lipid metabolism products exhibit a circadian rhythm as well. For example, circulating non-esterified fatty acids in humans are higher at night due to an increased lipolytic activity [ 29 ]. In addition, myocardial infarction episodes and asthma are associated with the circadian cycle of metabolism.

These attacks peak at night or early in the morning [ 30, 31 ]. In the early hours of the morning, the cardiovascular system improves in response to the activation of sympathetic nerve activity, and in the evening hours, blood pressure and heart rate peak.

Cardiac attacks, particularly early in the morning or in the evening, can be caused by this diurnal rhythm of the cardiovascular system.

The diurnal rhythm of hormones and some metabolic processes are shown in Figure 1. The diurnal rhythm of hormones and some metabolic processes. The release of leptin hormone occurs in a circadian cycle, and serum leptin levels peak at night.

The levels of growth hormone peak between and a. İnsulin secretion decrease at night especially between and a.

Synthesis and release of melatonin is stimulated in the dark at night, while it is suppressed by light during the day. Lipid absorption in the dark phase is higher than in the light phase.

Myocardial infarction peak at night or early in the morning. In mammals, circadian rhythms are controlled mainly by SCN, which are called the master clock. Suprachiasmatic nuclei consist of multiple, single-celled circadian oscillators located at the anterior hypothalamus region of the brain and produce coordinated circadian signals when synchronized [ 32 ].

Suprachiasmatic nuclei synapse directly with ventral and dorsal subventricular regions, cell bodies located in ventral and dorsal subventricular areas, and the dorsomedial hypothalamus. Even though these regions interact with one another, neurons located in the dorsal supraventricular region are more effective in regulating thermogenesis, whereas the ventral supraventricular region mainly plays a role in the regulation of sleep-wake and activity cycles.

In addition, the paraventricular hypothalamus is responsible for corticosteroid release, whereas the lateral hypothalamus is responsible for nutrition and alertness [ 33 ]. Suprachiasmatic nuclei have an important role in the regulation of glucose metabolism.

Insulin sensitivity and glucose uptake are impaired in rats with lesions in their SCN [ 36 ]. Deterioration in the circadian clock can lead to impaired insulin secretion and hypoinsulinemia [ 29 ]. Circadian rhythm-related CLOCK and BMAL1 proteins are involved in the production and release of insulin by binding to the circadian rhythm-regulating distal regions of pancreatic β-cells [ 37 ].

Both Type 1 and 2 diabetes have insulin insufficiency or absence due to β-cell damage. Therefore, the role of circadian rhythm in the etiology of diabetes should not be overlooked in terms of β-cell damage [ 38 ]. Clock genes and tasks regulating circadian rhythms in mammals are summarized in Table 1 [ 2 ].

Genes of the circadian rhythm and their roles [ 2 ]. In mammals, circadian clock homeostasis is enabled by feedback negative and feed-forward positive mechanisms influencing transcription, translation, and post-translational events [ 5, 29 ].

The transcriptional feedback pattern is mediated through the Cry1, Cry2, Per1, and Per2 proteins. The CLOCK and BMAL1 proteins bind to the E-promoter region on the Per and Cry genes and induce their expression. This negative feedback mechanism is important for the circadian system to work effectively.

The metabolic pathways that provide energy homeostasis are coordinated by metabolites that propose changes and proactively prepare the molecular environment as well as acute signaling systems that respond instantaneously to changes in circadian clocks [ 41 ].

These pathways have important interactions with the biological metabolism clock. The circadian clock can affect the function of hormone receptors peroxisome proliferator activated receptor [PPAR]α, PPARγ, and REV-ERBα and some genes at the cellular level sirtruin [ 41, 42 ].

Nuclear hormone receptors PPARα, PPARγ, REV-ERBα, RORα, HNF4α, TRα, and NURR1 and ligands present in metabolic tissues function as sensors that combine circadian and metabolic pathways [ 41 ].

For example, PPARs are a link between the circadian clock and energy metabolism. PPARγ localizes in adipose tissue and activates transcriptional factors that increase lipogenesis and lipid storage. PPARα from nuclear hormone receptors triggers ketogenesis and hepatic fatty acid oxidation in response to starvation.

PPARδ is the most prevalent nuclear cell receptor in the body and is able to correlate daily changes in body temperature with the circadian clock [ 43 ]. The rhythmic expression and activation of metabolic pathways are mainly associated with the coordination of clock genes BMAL1, Per2, Per1, Per3, Cry1, and Cry2 in liver and adipose tissues.

There is a link between BMAL1 protein, lipogenic pathways, and cellular clock mechanisms. REV-ERBα a transcriptional repressor of BMAL1 and RORα a positive regulator of BMAL1 are nuclear hormone receptors regulating lipogenesis.

Moreover, both are modulated by CLOCK: BMAL1. PPARα plays a role in lipid and lipoprotein metabolism. PPARα directly binds to the promoter region of the BMAL1 protein, which regulates the PPARα expression via the CLOCK: BMAL1 heterodimer [ 44 ].

Another factor that affects the circadian rhythm function is the sirtuin SIRT genes. There are 7 variations of the SIRT family SIRT 1—7. The regulation of gene expression is the most important mechanism influenced by the SIRT family.

SIRT1, SIRT6, and SIRT7 predominantly localize in the cell nucleus, SIRT2 in the cytoplasm, and SIRT3, SIRT4, and SIRT5 in the mitochondria.

SIRT1 plays a significant role in the regulation of metabolic processes such as insulin sensitivity, lipid metabolism, and gluconeogenesis, as well as human lifespan [ 45 ].

SIRT1 modulates CLOCK: BMAL1 activity and contributes to the circadian cycle. SIRT 3—5 genes regulate intracellular pathways such as fatty acid oxidation, ketogenesis, urea cycle, and oxidative phosphorylation [ 33 ]. Intracellular oxidation-reduction redox status is an important factor that regulates the clock genes in peripheral tissues.

CLOCK proteins can bind effectively only in the presence of reduced NADH and NADPH, BMAL1, and E-box sequences. When intracellular ATP levels are reduced, AMPK AMP-activating protein kinase functions as a food sensor and activates intracellular energy supply pathways.

The energy produced and stored in metabolism is used to maintain metabolic activities such as basal metabolic rate, physical activity, and thermal effect of foods [ 48 ]. Francis G Benedict first described the circadian changes in energy metabolism in [ 49 ]. Furthermore, Haugen et al.

One of the most important factors affecting the basal metabolic rate is the sleep pattern. Sleep and circadian rhythm are the main components of energy metabolism regulation [ 48, 51 ].

There are 2 phases of sleep: rapid eye movement REM and non-REM [ 52 ]. The sympathetic nervous system activity and dreams increase during the REM period. Body temperature, heart rate, respiratory rate, and blood pressure increase during REM.

Irregularities in the REM period increase due to the activity of the sympathetic nervous system [ 53 ]. Therefore, deterioration of the sleep cycle due to late sleeping, jet lag, shift work, and so on can lead to a decrease in the basal metabolic rate by altering the timing of the REM phase of sleep.

However, studies emphasize the different metabolic effects of exercise type, duration, and length. For example, a review study highlights that maximal performance in short-term anaerobic exercises occurs late in the afternoon, usually at noon [ 56 ], which also corresponds to the peak body temperature [ 56, 57 ].

There is a 0. Body temperature affects muscle activity [ 60 ]. This difference between the morning and evening hours can affect exercise performance and, indirectly, the basal metabolic rate. Meal time affects the physical performance.

Exercise before or after a meal has different effects on fatty acid oxidation and appetite metabolism [ ]. An approach to reduce body weight and facilitate fat loss is to perform postprandial aerobic exercise after an overnight fast [ 64 ]. Exercise during fasting causes the use of glycogen deposits to increase fat oxidation, and lowers plasma insulin by increasing plasma epinephrine and norepinephrine levels causing lipolysis.

On the contrary, some studies focused on the beneficial effects of postprandial exercise on body weight control compared to exercise during fasting because of its positive effects on appetite and resting metabolism [ 65 ].

A study found that a min of moderate exercise on a treadmill significantly increased the resting metabolic rate 40 min after eating a Mediterranean-style breakfast in the first 24 h [ 66 ]. In many studies, the total energy intake, dietary patterns, physical characteristics, and duration and severity of exercise are not similar, thereby leading to different interpretations of results.

Another component of total energy expenditure is the thermal effect of nutrients. The thermal effect of foods is influenced by the macronutrient composition of the diet. In addition, meal timing is an important factor affecting the thermal effect of foods. Diet-induced thermogenesis is higher in the morning hours compared to evening and night hours [ 68 ].

Similarly, in a study by Morris et al. The reduction in the thermal effect of foods from morning to evening may primarily be due to the effect of the endocrine circadian system on gastrointestinal physiology.

Intestinal motility in the morning hours is more effective than in the evening hours. Two studies on healthy adults revealed that the rate of gastric emptying in the morning 8.

was higher than in the evening 8. In addition, circadian rhythm disturbances, such as shift work and jet lag, cause gastrointestinal system disorders such as abdominal pain, bloating, diarrhea, or constipation. These observations reveal a functional correlation between daily rhythms and gastrointestinal physiology.

Hoogerwerf et al. Here, the impact of the circadian rhythm on energy expenditure components and its role in energy balance has been emphasized. However, some studies have shown that some environmental factors i.

The peripheral clocks play an integral and unique role in each of their respective tissues, driving the circadian expression of specific genes involved in a variety of physiological functions.

The existence of all these clocks working together and synchronized by the central clock, with many hormones and physiological or environmental variables changing during the day, make this bidirectional interaction on circadian system rather complicated [ 4 ].

Food is one of the external synchronizers of our peripheral clocks. The primary role of the circadian clock is to entrain the organism to the environmental cues; this allows the organisms to predict food availability.

Limiting food access to a particular time of the day has profound effects on the behavior and physiology of the organisms [ 72 ]. Damiola et al. Feeding time has a significant effect on the repertoire, phase, and amplitude of rhythmic gene expression.

In a study, it was shown that both temporal pattern of food intake and the circadian clock had an effect on hepatic gene transcription in wild-type mice [ 73 ].

The diet composition is another important factor that affects the circadian clock. Kohsaka et al. One of the notable non-photic cues for regulating the peripheral clock is exercise.

It is suggested that physical activity or exercise causes several physiological changes, such as body temperature and hormonal status changes, which are known to affect the peripheral clocks via sympathetic nervous activation and glucocorticoid release [ 75 ]. The elevation in body temperature may act as an input to the circadian pacemaker of mammals [ 77 ].

In addition, exercise promotes the production and release of melatonin. The beneficial effect of 4 weeks of melatonin treatment to modulate the circadian components of the sleep-wake cycle commonly results in improved sleep quality [ 78 ].

On the contrary, molecular circadian clock in peripheral tissues can respond to the time of exercise, suggesting that physical activity provides important timing information for the synchronization of circadian clocks throughout the body.

While the exact duration and intensity of exercise required to alter circadian rhythmicity has not been determined, one study in mice found that low-intensity endurance exercise sustained over the course of 2 h per day for 4 weeks was adequate enough to entrain the circadian clock and alter circadian rhythmicity [ 79 ].

Generally, when the peripheral clocks are desynchronized from the central clock, it results in chronodisruption [ 80 ]. This physiological alteration is related to different illnesses such as cancer, cardiovascular diseases, depression, obesity, and metabolic syndrome [ 72 ].

For example, in the treatment of obesity, the basic diet treatment approach is restricted energy intake [ 81 ]. Generally, factors that directly affect biological rhythms, such as meal times and sleeping times, are not routinely examined when diets are planned.

The circadian clock has an important role in energy homeostasis and metabolic processes. Therefore, the evaluation of factors shift work, irregular sleep, insomnia, etc.

For example, the HMG-COA enzyme, a cholesterol-rate limiting enzyme, shows a circadian rhythm in humans. This enzyme peaks at night, so it is recommended to take cholesterol-lowering drugs such as statins at night to maximize their effectiveness [ 19 ].

Chrononutrition is an approach to determine the optimal nutrient uptake to maintain health and regulate circadian rhythm [ 82 ]. For example, caffeine, nobiletin a flavonoid present in citrus fruits , and resveratrol in foods may cause circadian rhythm changes at molecular or behavioral levels [ 83 ].

Chronoexercise primarily investigates the effect of the length of exercise on the maintenance of health and athletic performance, rapid changes in the internal clock system, or re-regulation of the circadian clock [ 84 ]. As a result, circadian rhythm has a bidirectional interaction with almost all metabolic processes and is a primary factor affecting the sleep-wake cycle.

Therefore, questioning and utilizing sleep pattern, quality information, and creating treatment guidelines using circadian rhythm may increase the success of disease treatment. For this reason, novel approaches, perspectives, and treatment strategies in metabolic balance could be developed.

This article does not contain any studies with human participants or animals carried out by any of the authors. conducted the literature review and N.

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Metabolic Regulation of Circadian Rhythms. Circadian Rhythm and Energy Homeostasis. Effect of Circadian Rhythm on Energy Balance. Effect of Dietary Intake and Physical Activity on Circadian Rhythms. Statement of Ethics. Disclosure Statement. Funding Source. Author Contributions. Article Navigation.

Review Articles April 23 Effect of Circadian Rhythm on Metabolic Processes and the Regulation of Energy Balance. Subject Area: Endocrinology , Further Areas , Nutrition and Dietetics , Public Health. Yeliz Serin ; Yeliz Serin. Faculty of Health Sciences, Department of Nutrition and Dietetic, Gazi University, Ankara, Turkey.

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View large Download slide. Table 1. View large. View Large. The authors declare that they have no conflicts of interest. Akıncı E, Orhan FÖ. Sirkadiyen ritim uyku bozuklukları. Psikiyatr Guncel Yaklasimlar. Özbayer C, Değirmenci İ. Sirkadiyen saat, hücre döngüsü ve kanser.

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The scientists conducting this multiyear study want to know how prolonged changes to circadian rhythms—the internal processes that follow a roughly hour cycle—may affect metabolism and body weight in people who keep unconventional sleep-wake schedules, such as nurses, security guards, and pilots.

In a nearby lab at Beth Israel Deaconess Medical Center, Clifford Saper, MD, PhD, James Jackson Putnam Professor of Neurology and Neuroscience at Harvard Medical School, is leading a related metabolism experiment to observe how mice adapt to a hour schedule of light and darkness—four hours shorter than a normal day.

Saper and Duffy are among some 60 faculty in the HMS Division of Sleep Medicine contributing to the growing body of knowledge about sleep, circadian rhythms, and health. Along with metabolism and sleep patterns, the circadian system influences many important functions, including heart rate, blood pressure, body temperature, hormone levels, and urine production.

Circadian disruptions and lack. of sleep have been associated with serious health problems ranging from cancer to obesity to depression. Found in most living organisms, circadian rhythms are regulated by light, behavior, and a biological clock mechanism—a set of clock genes located in cells throughout the body.

Even daily routines, such as reading our smartphones before bed, can interfere with our circadian rhythms. There has been some success in translating this understanding into identifying pharmacological targets and molecular therapeutics. However, owing to the complexity of how the internal clock mechanisms work, and the extensive crosstalk and feedback loops that maintain homeostasis, a large portion of the internal clock mechanisms are still undruggable and under-exploited.

Recent advances made in applying systems biology and systems pharmacology approaches can help in gaining a more in-depth understanding of the circadian circuitry and its down-stream effects, which could translate into identifying molecular targets for the treatment of different diseases.

In addition, this in-depth understanding is important for making relevant life-style interventions that modulate the external cues capable of regulating the internal clock, and hence help prevent or manage circadian disruption related disorders. Skene DJ, Arendt J Human circadian rhythms: physiological and therapeutic relevance of light and melatonin.

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Correspondence to Vivaswath S. Ayyar or Siddharth Sukumaran. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Reprints and permissions. Ayyar, V. Circadian rhythms: influence on physiology, pharmacology, and therapeutic interventions.

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Download PDF. Abstract Circadian rhythms are ubiquitous phenomena that recur daily in a self-sustaining, entrainable, and oscillatory manner, and orchestrate a wide range of molecular, physiological, and behavioral processes. Migraine: from pathophysiology to treatment Article Open access 08 April Daridorexant treatment for chronic insomnia: a real-world retrospective single-center study Article Open access 27 January Cannabis, Cannabinoids, and Sleep: a Review of the Literature Article 27 March Use our pre-submission checklist Avoid common mistakes on your manuscript.

Introduction Circadian biorhythms are ubiquitous phenomena that recur daily in a self-sustaining, entrainable, and oscillatory manner in most organisms.

The circadian clock system Circadian clocks comprise a hierarchical network of central and peripheral clocks which generate, sustain, and synchronize circadian rhythms.