A circadian rhythm (/sɜːrˈkeɪdiən/) is any biological process that displays an endogenous, entrainable oscillation of about 24 hours. These 24-hour rhythms are driven by a circadian clock, and they have been widely observed in plants, animals, fungi, and cyanobacteria.
The term circadian comes from the Latin circa, meaning "around" (or "approximately"), and diēm, meaning "day". The formal study of biological temporal rhythms, such as daily, tidal, weekly, seasonal, and annual rhythms, is called chronobiology. Processes with 24-hour oscillations are more generally called diurnal rhythms; strictly speaking, they should not be called circadian rhythms unless their endogenous nature is confirmed.
Although circadian rhythms are endogenous ("built-in", self-sustained), they are adjusted (entrained) to the local environment by external cues called zeitgebers (from German, "time giver"), which include light, temperature and redox cycles. In medical science, an abnormal circadian rhythm in humans is known as circadian rhythm disorder.
In 2017, the Nobel Prize in Physiology or Medicine was awarded to Jeffrey C. Hall, Michael Rosbash and Michael W. Young "for their discoveries of molecular mechanisms controlling the circadian rhythm" in fruit flies.
Some features of the human circadian (24-hour) biological clock
The earliest recorded account of a circadian process dates from the 4th century BC, when Androsthenes, a ship captain serving under Alexander the Great, described diurnal leaf movements of the tamarind tree. The observation of a circadian or diurnal process in humans is mentioned in Chinese medical texts dated to around the 13th century, including the Noon and Midnight Manual and the Mnemonic Rhyme to Aid in the Selection of Acu-points According to the Diurnal Cycle, the Day of the Month and the Season of the Year.
The first recorded observation of an endogenous circadian oscillation was by the French scientist Jean-Jacques d'Ortous de Mairan in 1729. He noted that 24-hour patterns in the movement of the leaves of the plant Mimosa pudica continued even when the plants were kept in constant darkness, in the first experiment to attempt to distinguish an endogenous clock from responses to daily stimuli.
In 1896, Patrick and Gilbert observed that during a prolonged period of sleep deprivation, sleepiness increases and decreases with a period of approximately 24 hours. In 1918, J.S. Szymanski showed that animals are capable of maintaining 24-hour activity patterns in the absence of external cues such as light and changes in temperature. In the early 20th century, circadian rhythms were noticed in the rhythmic feeding times of bees. Extensive experiments were done by Auguste Forel, Ingeborg Beling, and Oskar Wahl to see whether this rhythm was due to an endogenous clock. The existence of circadian rhythm was independently discovered in the fruit fly Drosophila melanogaster in 1935 by two German zoologists, Hans Kalmus and Erwin Bünning.
In 1954, an important experiment was reported by Colin Pittendrigh who showed that eclosion (the process of pupa turning into adult) in D. pseudoobscura was a circadian behaviour. He demonstrated that while temperature played a vital role in eclosion rhythm, the period of eclosion was delayed but not stopped when temperature was decreased. It was an indication that circadian rhythm was controlled by an internal biological clock. The term circadian was coined by Franz Halberg in 1959. According to Halberg's original definition:
The term "circadian" was derived from circa (about) and dies (day); it may serve to imply that certain physiologic periods are close to 24 hours, if not exactly that length. Herein, "circadian" might be applied to all "24-hour" rhythms, whether or not their periods, individually or on the average, are different from 24 hours, longer or shorter, by a few minutes or hours.
In 1977, the International Committee on Nomenclature of the International Society for Chronobiology formally adopted the definition, which states:
Circadian: relating to biologic variations or rhythms with a frequency of 1 cycle in 24 ± 4 h; circa (about, approximately) and dies (day or 24 h). Note: term describes rhythms with an about 24-h cycle length, whether they are frequency-synchronized with (acceptable) or are desynchronized or free-running from the local environmental time scale, with periods of slightly yet consistently different from 24-h.
Ron Konopka and Seymour Benzer identified the first clock mutant in Drosophila in 1971 and called it "period" (per) gene, the first discovered genetic determinant of behavioral rhythmicity. per gene was isolated in 1984 by two teams of researchers. Konopka, Jeffrey Hall, Michael Roshbash and their team showed that per locus is the centre of the circadian rhythm, and that loss of per stops circadian activity. At the same time, Michael W. Young's team reported similar effects of per, and that the gene covers 7.1-kilobase (kb) interval on the X chromosome and encodes a 4.5-kb poly(A)+ RNA. They went on to discover the key genes and neurones in Drosophila circadian system, for which Hall, Rosbash and Young received the Nobel Prize in Physiology or Medicine 2017.
Joseph Takahashi discovered the first mammalian circadian clock mutation (clockΔ19) using mice in 1994. However, recent studies show that deletion of clock does not lead to a behavioral phenotype (the animals still have normal circadian rhythms), which questions its importance in rhythm generation.
To be called circadian, a biological rhythm must meet these three general criteria:
Circadian rhythms allow organisms to anticipate and prepare for precise and regular environmental changes. They thus enable organisms to better capitalize on environmental resources (e.g. light and food) compared to those that cannot predict such availability. It has therefore been suggested that circadian rhythms put organisms at a selective advantage in evolutionary terms. However, rhythmicity appears to be as important in regulating and coordinating internal metabolic processes, as in coordinating with the environment. This is suggested by the maintenance (heritability) of circadian rhythms in fruit flies after several hundred generations in constant laboratory conditions, as well as in creatures in constant darkness in the wild, and by the experimental elimination of behavioral, but not physiological, circadian rhythms in quail.
What drove circadian rhythms to evolve has been an enigmatic question. Previous hypotheses emphasized that photosensitive proteins and circadian rhythms may have originated together in the earliest cells, with the purpose of protecting replicating DNA from high levels of damaging ultraviolet radiation during the daytime. As a result, replication was relegated to the dark. However, evidence for this is lacking, since the simplest organisms with a circadian rhythm, the cyanobacteria, do the opposite of this - they divide more in the daytime. Recent studies instead highlight the importance of co-evolution of redox proteins with circadian oscillators in all three domains of life following the Great Oxidation Event approximately 2.3 billion years ago. The current view is that circadian changes in environmental oxygen levels and the production of reactive oxygen species (ROS) in the presence of daylight are likely to have driven a need to evolve circadian rhythms to preempt, and therefore counteract, damaging redox reactions on a daily basis.
The simplest known circadian clocks are bacterial circadian rhythms, exemplified by the prokaryote cyanobacteria. Recent research has demonstrated that the circadian clock of Synechococcus elongatus can be reconstituted in vitro with just the three proteins (KaiA, KaiB, KaiC) of their central oscillator. This clock has been shown to sustain a 22-hour rhythm over several days upon the addition of ATP. Previous explanations of the prokaryotic circadian timekeeper were dependent upon a DNA transcription/translation feedback mechanism.
A defect in the human homologue of the Drosophila "period" gene was identified as a cause of the sleep disorder FASPS (Familial advanced sleep phase syndrome), underscoring the conserved nature of the molecular circadian clock through evolution. Many more genetic components of the biological clock are now known. Their interactions result in an interlocked feedback loop of gene products resulting in periodic fluctuations that the cells of the body interpret as a specific time of the day.
It is now known that the molecular circadian clock can function within a single cell; i.e., it is cell-autonomous. This was shown by Gene Block in isolated mollusk BRNs. At the same time, different cells may communicate with each other resulting in a synchronised output of electrical signaling. These may interface with endocrine glands of the brain to result in periodic release of hormones. The receptors for these hormones may be located far across the body and synchronise the peripheral clocks of various organs. Thus, the information of the time of the day as relayed by the eyes travels to the clock in the brain, and, through that, clocks in the rest of the body may be synchronised. This is how the timing of, for example, sleep/wake, body temperature, thirst, and appetite are coordinately controlled by the biological clock.
Circadian rhythmicity is present in the sleeping and feeding patterns of animals, including human beings. There are also clear patterns of core body temperature, brain wave activity, hormone production, cell regeneration, and other biological activities. In addition, photoperiodism, the physiological reaction of organisms to the length of day or night, is vital to both plants and animals, and the circadian system plays a role in the measurement and interpretation of day length. Timely prediction of seasonal periods of weather conditions, food availability, or predator activity is crucial for survival of many species. Although not the only parameter, the changing length of the photoperiod ('daylength') is the most predictive environmental cue for the seasonal timing of physiology and behavior, most notably for timing of migration, hibernation, and reproduction.
Mutations or deletions of clock gene in mice have demonstrated the importance of body clocks to ensure the proper timing of cellular/metabolic events; clock-mutant mice are hyperphagic and obese, and have altered glucose metabolism. In mice, deletion of the Rev-ErbA alpha clock gene facilitates diet-induced obesity and changes the balance between glucose and lipid utilization predisposing to diabetes. However, it is not clear whether there is a strong association between clock gene polymorphisms in humans and the susceptibility to develop the metabolic syndrome.
The rhythm is linked to the light–dark cycle. Animals, including humans, kept in total darkness for extended periods eventually function with a free-running rhythm. Their sleep cycle is pushed back or forward each "day", depending on whether their "day", their endogenous period, is shorter or longer than 24 hours. The environmental cues that reset the rhythms each day are called zeitgebers (from the German, "time-givers"). Totally blind subterranean mammals, e.g., blind mole rat Spalax sp., are able to maintain their endogenous clocks in the apparent absence of external stimuli. Although they lack image-forming eyes, their photoreceptors (which detect light) are still functional; they do surface periodically as well.
Free-running organisms that normally have one or two consolidated sleep episodes will still have them when in an environment shielded from external cues, but the rhythm is not entrained to the 24-hour light–dark cycle in nature. The sleep–wake rhythm may, in these circumstances, become out of phase with other circadian or ultradian rhythms such as metabolic, hormonal, CNS electrical, or neurotransmitter rhythms.
Norwegian researchers at the University of Tromsø have shown that some Arctic animals (ptarmigan, reindeer) show circadian rhythms only in the parts of the year that have daily sunrises and sunsets. In one study of reindeer, animals at 70 degrees North showed circadian rhythms in the autumn, winter and spring, but not in the summer. Reindeer on Svalbard at 78 degrees North showed such rhythms only in autumn and spring. The researchers suspect that other Arctic animals as well may not show circadian rhythms in the constant light of summer and the constant dark of winter.
A 2006 study in northern Alaska found that day-living ground squirrels and nocturnal porcupines strictly maintain their circadian rhythms through 82 days and nights of sunshine. The researchers speculate that these two rodents notice that the apparent distance between the sun and the horizon is shortest once a day, and, thus, a sufficient signal to entrain (adjust) by.
The navigation of the fall migration of the Eastern North American monarch butterfly (Danaus plexippus) to their overwintering grounds in central Mexico uses a time-compensated sun compass that depends upon a circadian clock in their antennae. Also, circadian rhythm is also known to control mating behavior in certain moth species such as Spodoptera littoralis, where females produce specific pheromone that attracts and resets the male circadian rhythm to induce mating at night.
Plant circadian rhythms tell the plant what season it is and when to flower for the best chance of attracting pollinators. Behaviors showing rhythms include leaf movement, growth, germination, stomatal/gas exchange, enzyme activity, photosynthetic activity, and fragrance emission, among others. Circadian rhythms occur as a plant entrains to synchronize with the light cycle of its surrounding environment. These rhythms are endogenously generated and self-sustaining and are relatively constant over a range of ambient temperatures. Important features include two interacting transcription-translation feedback loops: proteins containing PAS domains, which facilitate protein-protein interactions; and several photoreceptors that fine-tune the clock to different light conditions. Anticipation of changes in the environment allows appropriate changes in a plant's physiological state, conferring an adaptive advantage. A better understanding of plant circadian rhythms has applications in agriculture, such as helping farmers stagger crop harvests to extend crop availability and securing against massive losses due to weather.
Light is the signal by which plants synchronize their internal clocks to their environment and is sensed by a wide variety of photoreceptors. Red and blue light are absorbed through several phytochromes and cryptochromes. One phytochrome, phyA, is the main phytochrome in seedlings grown in the dark but rapidly degrades in light to produce Cry1. Phytochromes B–E are more stable with phyB, the main phytochrome in seedlings grown in the light. The cryptochrome (cry) gene is also a light-sensitive component of the circadian clock and is thought to be involved both as a photoreceptor and as part of the clock's endogenous pacemaker mechanism. Cryptochromes 1–2 (involved in blue–UVA) help to maintain the period length in the clock through a whole range of light conditions.
The central oscillator generates a self-sustaining rhythm and is driven by two interacting feedback loops that are active at different times of day. The morning loop consists of CCA1 (Circadian and Clock-Associated 1) and LHY (Late Elongated Hypocotyl), which encode closely related MYB transcription factors that regulate circadian rhythms in Arabidopsis, as well as PRR 7 and 9 (Pseudo-Response Regulators.) The evening loop consists of GI (Gigantea) and ELF4, both involved in regulation of flowering time genes. When CCA1 and LHY are overexpressed (under constant light or dark conditions), plants become arrhythmic, and mRNA signals reduce, contributing to a negative feedback loop. Gene expression of CCA1 and LHY oscillates and peaks in the early morning, whereas TOC1 gene expression oscillates and peaks in the early evening. While it was previously hypothesised that these three genes model a negative feedback loop in which over-expressed CCA1 and LHY repress TOC1 and over-expressed TOC1 is a positive regulator of CCA1 and LHY, it was shown in 2012 by Andrew Millar and others that TOC1 in fact serves as a repressor not only of CCA1, LHY, and PRR7 and 9 in the morning loop but also of GI and ELF4 in the evening loop. This finding and further computational modeling of TOC1 gene functions and interactions suggest a reframing of the plant circadian clock as a triple negative-component repressilator model rather than the positive/negative-element feedback loop characterizing the clock in mammals.
In 2018, researchers found that the expression of PRR5 and TOC1 hnRNA nascent transcripts follows the same oscillatory pattern as processed mRNA transcripts rhythmically in A.thaliana.LNKs binds to the 5'region of PRR5 and TOC1 and interacts with RNAP II and other transcription factors.Moreover,RVE8-LNKs interaction enables a permissive histone-methylation pattern(H3K4me3) to be modified and the histone-modification itself parallels the oscillation of clock gene expression.
The molecular mechanism of circadian rhythm and light perception are best understood in Drosophila. Clock genes are discovered from Drosophila, and they act together with the clock neurones. There are two unique rhythms, one during the process of hatching (called eclosion) from the pupa, and the other during mating. The clock neurones are located in distinct clusters in the central brain. The best-understood clock neurones are the large and small lateral ventral neurons (l-LNvs and s-LNvs) of the optic lobe. These neurones produce pigment dispersing factor (PDF), a neuropeptide that acts as a circadian neuromodulator between different clock neurones.
Drosophila circadian rhythm is through a transcription-translation feedback loop. The core clock mechanism consists of two interdependent feedback loops, namely the PER/TIM loop and the CLK/CYC loop. The CLK/CYC loop occurs during the day and initiates the transcription of the per and tim genes. But their proteins levels remain low until dusk, because during daylight also activates the doubletime (dbt) gene. DBT protein causes phosphorylation and turnover of monomeric PER proteins. TIM is also phosphorylated by shaggy until sunset. After sunset, DBT disappears, so that PER molecules stably bind to TIM. PER/TIM dimer enters the nucleus several at night, and binds to CLK/CYC dimers. Bound PER completely stops the transcriptional activity of CLK and CYC.
In the early morning, light activates the cry gene and its protein CRY causes the breakdown of TIM. Thus PER/TIM dimer dissociates, and the unbound PER becomes unstable. PER undergoes progressive phosphorylation and ultimately degradation. Absence of PER and TIM allows activation of clk and cyc genes. Thus, the clock is reset to start the next circadian cycle.
The primary circadian clock in mammals is located in the suprachiasmatic nucleus (or nuclei) (SCN), a pair of distinct groups of cells located in the hypothalamus. Destruction of the SCN results in the complete absence of a regular sleep–wake rhythm. The SCN receives information about illumination through the eyes. The retina of the eye contains "classical" photoreceptors ("rods" and "cones"), which are used for conventional vision. But the retina also contains specialized ganglion cells that are directly photosensitive, and project directly to the SCN, where they help in the entrainment (synchronization) of this master circadian clock.
These cells contain the photopigment melanopsin and their signals follow a pathway called the retinohypothalamic tract, leading to the SCN. If cells from the SCN are removed and cultured, they maintain their own rhythm in the absence of external cues.
The SCN takes the information on the lengths of the day and night from the retina, interprets it, and passes it on to the pineal gland, a tiny structure shaped like a pine cone and located on the epithalamus. In response, the pineal secretes the hormone melatonin.Secretion of melatonin peaks at night and ebbs during the day and its presence provides information about night-length.
Several studies have indicated that pineal melatonin feeds back on SCN rhythmicity to modulate circadian patterns of activity and other processes. However, the nature and system-level significance of this feedback are unknown.
The circadian rhythms of humans can be entrained to slightly shorter and longer periods than the Earth's 24 hours. Researchers at Harvard have shown that human subjects can at least be entrained to a 23.5-hour cycle and a 24.65-hour cycle (the latter being the natural solar day-night cycle on the planet Mars).
Early research into circadian rhythms suggested that most people preferred a day closer to 25 hours when isolated from external stimuli like daylight and timekeeping. However, this research was faulty because it failed to shield the participants from artificial light. Although subjects were shielded from time cues (like clocks) and daylight, the researchers were not aware of the phase-delaying effects of indoor electric lights. The subjects were allowed to turn on light when they were awake and to turn it off when they wanted to sleep. Electric light in the evening delayed their circadian phase. A more stringent study conducted in 1999 by Harvard University estimated the natural human rhythm to be closer to 24 hours and 11 minutes: much closer to the solar day.
The classic phase markers for measuring the timing of a mammal's circadian rhythm are:
For temperature studies, subjects must remain awake but calm and semi-reclined in near darkness while their rectal temperatures are taken continuously. Though variation is great among normal chronotypes, the average human adult's temperature reaches its minimum at about 05:00 (5 a.m.), about two hours before habitual wake time. Baehr et al. found that, in young adults, the daily body temperature minimum occurred at about 04:00 (4 a.m.) for morning types but at about 06:00 (6 a.m.) for evening types. This minimum occurred at approximately the middle of the eight-hour sleep period for morning types, but closer to waking in evening types.
Melatonin is absent from the system or undetectably low during daytime. Its onset in dim light, dim-light melatonin onset (DLMO), at roughly 21:00 (9 p.m.) can be measured in the blood or the saliva. Its major metabolite can also be measured in morning urine. Both DLMO and the midpoint (in time) of the presence of the hormone in the blood or saliva have been used as circadian markers. However, newer research indicates that the melatonin offset may be the more reliable marker. Benloucif et al. found that melatonin phase markers were more stable and more highly correlated with the timing of sleep than the core temperature minimum. They found that both sleep offset and melatonin offset are more strongly correlated with phase markers than the onset of sleep. In addition, the declining phase of the melatonin levels is more reliable and stable than the termination of melatonin synthesis.
Other physiological changes that occur according to a circadian rhythm include heart rate and many cellular processes "including oxidative stress, cell metabolism, immune and inflammatory responses, epigenetic modification, hypoxia/hyperoxia response pathways, endoplasmic reticular stress, autophagy, and regulation of the stem cell environment." In a study of young men, it was found that the heart rate reaches its lowest average rate during sleep, and its highest average rate shortly after waking.
In contradiction to previous studies, it has been found that there is no effect of body temperature on performance on psychological tests. This is likely due to evolutionary pressures for higher cognitive function compared to the other areas of function examined in previous studies.
More-or-less independent circadian rhythms are found in many organs and cells in the body outside the suprachiasmatic nuclei (SCN), the "master clock". Indeed, neuroscientist Joseph Takahashi and colleagues stated in a 2013 article that "almost every cell in the body contains a circadian clock." For example, these clocks, called peripheral oscillators, have been found in the adrenal gland, oesophagus, lungs, liver, pancreas, spleen, thymus, and skin. There is also some evidence that the olfactory bulb and prostate may experience oscillations, at least when cultured.
Though oscillators in the skin respond to light, a systemic influence has not been proven. In addition, many oscillators, such as liver cells, for example, have been shown to respond to inputs other than light, such as feeding.
Light resets the biological clock in accordance with the phase response curve (PRC). Depending on the timing, light can advance or delay the circadian rhythm. Both the PRC and the required illuminance vary from species to species and lower light levels are required to reset the clocks in nocturnal rodents than in humans.
Studies by Nathaniel Kleitman in 1938 and by Derk-Jan Dijk and Charles Czeisler in the 1990s put human subjects on enforced 28-hour sleep–wake cycles, in constant dim light and with other time cues suppressed, for over a month. Because normal people cannot entrain to a 28-hour day in dim light if at all, this is referred to as a forced desynchrony protocol. Sleep and wake episodes are uncoupled from the endogenous circadian period of about 24.18 hours and researchers are allowed to assess the effects of circadian phase on aspects of sleep and wakefulness including sleep latency and other functions - both physiological, behavioral, and cognitive.
A number of studies have concluded that a short period of sleep during the day, a power-nap, does not have any measurable effect on normal circadian rhythms but can decrease stress and improve productivity.
Health problems can result from a disturbance to the circadian rhythm. Circadian rhythms also play a part in the reticular activating system, which is crucial for maintaining a state of consciousness. A reversal in the sleep–wake cycle may be a sign or complication of uremia, azotemia or acute renal failure.
Lighting requirements for circadian regulation are not simply the same as those for vision; planning of indoor lighting in offices and institutions is beginning to take this into account. Animal studies on the effects of light in laboratory conditions have until recently considered light intensity (irradiance) but not color, which can be shown to "act as an essential regulator of biological timing in more natural settings".
Obesity and diabetes are associated with lifestyle and genetic factors. Among those factors, disruption of the circadian clockwork and/or misalignment of the circadian timing system with the external environment (e.g., light-dark cycle) might play a role in the development of metabolic disorders.
Shift-work or chronic jet-lag have profound consequences on circadian and metabolic events in the body. Animals that are forced to eat during their resting period show increased body mass and altered expression of clock and metabolic genes. In humans, shift-work that favors irregular eating times is associated with altered insulin sensitivity and higher body mass. Shift-work also leads to increased metabolic risks for cardio-metabolic syndrome, hypertension, and inflammation.
Due to the work nature of airline pilots, who often cross several timezones and regions of sunlight and darkness in one day, and spend many hours awake both day and night, they are often unable to maintain sleep patterns that correspond to the natural human circadian rhythm; this situation can easily lead to fatigue. The NTSB cites this as contributing to many accidents and has conducted several research studies in order to find methods of combating fatigue in pilots.
A number of other disorders, for example bipolar disorder and some sleep disorders such as delayed sleep phase disorder (DSPD), are associated with irregular or pathological functioning of circadian rhythms.
Disruption to rhythms in the longer term is believed to have significant adverse health consequences on peripheral organs outside the brain, in particular in the development or exacerbation of cardiovascular disease. Blue LED lighting suppresses melatonin production five times more than the orange-yellow high-pressure sodium (HPS) light; a metal halide lamp, which is white light, suppresses melatonin at a rate more than three times greater than HPS. Depression symptoms from long term nighttime light exposure can be undone by returning to a normal cycle.
Studies conducted on both animals and humans show major bidirectional relationships between the circadian system and abusive drugs. It is indicated that these abusive drugs affect the central circadian pacemaker. Individuals suffering from substance abuse display disrupted rhythms. These disrupted rhythms can increase the risk for substance abuse and relapse. It is possible that genetic and/or environmental disturbances to the normal sleep and wake cycle can increase the susceptibility to addiction.
It is difficult to determine if a disturbance in the circadian rhythm is at fault for an increase in prevalence for substance abuse or if other environmental factors such as stress are to blame. Changes to the circadian rhythm and sleep occur once an individual begins abusing drugs and alcohol. Once an individual chooses to stop using drugs and alcohol, the circadian rhythm continues to be disrupted.
The stabilization of sleep and the circadian rhythm might possibly help to reduce the vulnerability to addiction and reduce the chances of relapse.
Circadian rhythms and clock genes expressed in brain regions outside the suprachiasmatic nucleus may significantly influence the effects produced by drugs such as cocaine. Moreover, genetic manipulations of clock genes profoundly affect cocaine's actions.
In 2017, Jeffrey C. Hall, Michael W. Young, and Michael Rosbash were awarded Nobel Prize in Physiology or Medicine "for their discoveries of molecular mechanisms controlling the circadian rhythm".
Eventually I reverted, for the same reason, to "circadian" ...
...så det ikke ut til at reinen hadde noen døgnrytme om sommeren. Svalbardreinen hadde det heller ikke om vinteren.
Would local animals maintained under natural continuous daylight demonstrate the Aschoff effect described in previously published laboratory experiments using continuous light, in which rats' circadian activity patterns changed systematically to a longer period, expressing a 26-hour day of activity and rest?
6-Hydroxymelatonin (6-OHM) is a naturally occurring, endogenous, major active metabolite of melatonin. Similar to melatonin, 6-OHM is a full agonist of the MT1 and MT2 receptors. It is also an antioxidant and neuroprotective, and is even more potent in this regard relative to melatonin.Advanced sleep phase disorder
Advanced sleep phase disorder (ASPD), also known as the advanced sleep-phase type (ASPT) of circadian rhythm sleep disorder or advanced sleep phase syndrome (ASPS), is a condition in which patients feel very sleepy and go to bed early in the evening (e.g. 6:00–8:00 p.m.) and wake up very early in the morning (e.g. around 3:00 a.m.).Biphasic and polyphasic sleep
Biphasic sleep (or diphasic, bimodal or bifurcated sleep) is the practice of sleeping during two periods over 24 hours, while polyphasic sleep refers to sleeping multiple times – usually more than two. Each of these is in contrast to monophasic sleep, which is one period of sleep over 24 hours. Segmented sleep and divided sleep may refer to polyphasic or biphasic sleep, but may also refer to interrupted sleep, where the sleep has one or several shorter periods of wakefulness. A common form of biphasic or polyphasic sleep includes a nap, which is a short period of sleep, typically taken between the hours of 9 am and 9 pm as an adjunct to the usual nocturnal sleep period.
The term polyphasic sleep was first used in the early 20th century by psychologist J. S. Szymanski, who observed daily fluctuations in activity patterns (see Stampi 1992). It does not imply any particular sleep schedule. The circadian rhythm disorder known as irregular sleep-wake syndrome is an example of polyphasic sleep in humans. Polyphasic sleep is common in many animals, and is believed to be the ancestral sleep state for mammals, although simians are monophasic.The term polyphasic sleep is also used by an online community that experiments with alternative sleeping schedules to achieve more time awake each day. However, researchers such as Piotr Woźniak warn that such forms of sleep deprivation are not healthy. While many claim that polyphasic sleep was widely used by some polymaths and prominent people such as Leonardo da Vinci, Napoleon, and Nikola Tesla, there are few reliable sources supporting that view.Chronobiology
Chronobiology is a field of biology that examines periodic (cyclic) phenomena in living organisms and their adaptation to solar- and lunar-related rhythms. These cycles are known as biological rhythms. Chronobiology comes from the ancient Greek χρόνος (chrónos, meaning "time"), and biology, which pertains to the study, or science, of life. The related terms chronomics and chronome have been used in some cases to describe either the molecular mechanisms involved in chronobiological phenomena or the more quantitative aspects of chronobiology, particularly where comparison of cycles between organisms is required.
Chronobiological studies include but are not limited to comparative anatomy, physiology, genetics, molecular biology and behavior of organisms within biological rhythms mechanics. Other aspects include epigenetics, development, reproduction, ecology and evolution.Circadian rhythm sleep disorder
Circadian rhythm sleep disorders (CRSD) are a family of sleep disorders affecting (among other bodily processes) the timing of sleep. People with circadian rhythm sleep disorders are unable to go to sleep and awaken at the times commonly required for work and school as well as social needs. They are generally able to get enough sleep if allowed to sleep and wake at the times dictated by their "body clocks". The quality of their sleep is usually normal unless they also have another sleep disorder.
Humans, like most living organisms, have various biological rhythms. Circadian rhythms, often referred to as the body clock or the biological clock, control processes that re-occur daily, e.g. body temperature, alertness, and hormone secretion as well as sleep timing. Due to the circadian clock, sleepiness does not continuously increase throughout the day; a person's desire and ability to fall asleep is influenced both by the length of time since the person woke from an adequate sleep and by internal circadian rhythms. Thus, a person's body is ready for sleep and for wakefulness at relatively specific times of the day.
Sleep researcher Yaron Dagan states that "[t]hese disorders can lead to harmful psychological and functional difficulties and are often misdiagnosed and incorrectly treated due to the fact that doctors are unaware of their existence".Delayed sleep phase disorder
Delayed sleep phase disorder (DSPD), more often known as delayed sleep phase syndrome and also as delayed sleep-wake phase disorder, is a chronic dysregulation of a person's circadian rhythm (biological clock), compared to those of the general population and societal norms. The disorder affects the timing of sleep, peak period of alertness, the core body temperature rhythm, and hormonal and other daily cycles. People with DSPD generally fall asleep some hours after midnight and have difficulty waking up in the morning. People with DSPD probably have a circadian period significantly longer than 24 hours. Depending on the severity, the symptoms can be managed to a greater or lesser degree, but no cure is known, and research suggests a genetic origin for the disorder.
Affected people often report that while they do not get to sleep until the early morning, they do fall asleep around the same time every day. Unless they have another sleep disorder such as sleep apnea in addition to DSPD, patients can sleep well and have a normal need for sleep. However, they find it very difficult to wake up in time for a typical school or work day. If they are allowed to follow their own schedules, e.g. sleeping from 4:00 am to 1:00 pm, their sleep is improved and they may not experience excessive daytime sleepiness. Attempting to force oneself onto daytime society's schedule with DSPD has been compared to constantly living with jet lag; DSPD has, in fact, been referred to as "social jet lag".Researchers in 2017 linked DSPD to at least one genetic mutation. The syndrome usually develops in early childhood or adolescence. An adolescent version may disappear in late adolescence or early adulthood; otherwise, DSPD is a lifelong condition. Prevalence among adults is around 5–15% (50–150 in 1,000 adults). Prevalence among adolescents is as much as 7–16%.DSPD was first formally described in 1981 by Elliot D. Weitzman and others at Montefiore Medical Center. It is responsible for 7–13% of patient complaints of chronic insomnia. However, since many doctors are unfamiliar with the condition, it often goes untreated or is treated inappropriately; DSPD is often misdiagnosed as primary insomnia or as a psychiatric condition. DSPD can be treated or helped in some cases by careful daily sleep practices, morning light therapy, evening dark therapy, earlier exercise and meal times, and medications such as melatonin and modafinil; the former is a natural neurohormone partly responsible for the human body clock. At its most severe and inflexible, DSPD is a disability. A chief difficulty of treating DSPD is in maintaining an earlier schedule after it has been established, as the patient's body has a strong tendency to reset the sleeping schedule to its intrinsic late times. People with DSPD may improve their quality of life by choosing careers that allow late sleeping times, rather than forcing themselves to follow a conventional 9-to-5 work schedule.Diurnality
Diurnality is a form of plant or animal behavior characterized by activity during daytime, with a period of sleeping or other inactivity at night. The common adjective used for daytime activity is "diurnal." The timing of activity by an animal depends on a variety of environmental factors such as the temperature, the ability to gather food by sight, the risk of predation, and the time of year. Diurnality is a cycle of activity within a 24-hour period; cyclic activities called circadian rhythms are endogenous cycles not dependent on external cues or environmental factors. Animals active during twilight are crepuscular, those active during the night are nocturnal, and animals active at sporadic times during both night and day are cathemeral.
Plants that open their flowers during the daytime are described as diurnal, while those that bloom during nighttime are nocturnal. The timing of flower opening is often related to the time at which preferred pollinators are foraging. For example, sunflowers open during the day to attract bees, whereas the night-blooming cereus opens at night to attract large sphinx moths.Irregular sleep–wake rhythm
Irregular sleep–wake rhythm is a rare form of circadian rhythm sleep disorder. It is characterized by numerous naps throughout the 24-hour period, no main nighttime sleep episode and irregularity from day to day. Sufferers have no pattern of when they are awake or asleep, may have poor quality sleep, and often may be very sleepy while they are awake.
The total time asleep per 24 hours is normal for the person's age. The disorder is serious—an invisible disability. It can create social, familial, and work problems, making it hard for a person to maintain relationships and responsibilities, and may make a person home-bound and isolated.Jet lag
Jet lag is a physiological condition which results from alterations to the body's circadian rhythms caused by rapid long-distance trans-meridian (east–west or west–east) travel. For example, someone flying from New York to London, i.e. from west to east, feels as if the time were five hours earlier than local time, and someone travelling from London to New York, i.e. from east to west, feels as if the time were five hours later than local time. Jet lag was previously classified as one of the circadian rhythm sleep disorders.The condition of jet lag may last several days before the traveller is fully adjusted to the new time zone; a recovery period of one day per time zone crossed is a suggested guideline. Jet lag is especially an issue for airline pilots, aircraft crew, and frequent travellers. Airlines have regulations aimed at combating pilot fatigue caused by jet lag.
The term "jet lag" is used because before the arrival of passenger jet aircraft, it was uncommon to travel far and fast enough to cause desynchronosis. Travel by propeller-driven aircraft, by ship, or by train was slower and of more limited distance than jet flights, and thus did not contribute widely to the issue.Light therapy
Light therapy—or phototherapy, classically referred to as heliotherapy—consists of exposure to daylight or to specific wavelengths of light using polychromatic polarised light, lasers, light-emitting diodes, fluorescent lamps, dichroic lamps or very bright, full-spectrum light. The light is administered for a prescribed amount of time and, in some cases, at a specific time of day.
One common use of the term is associated with the treatment of skin disorders, chiefly psoriasis, acne vulgaris, eczema and neonatal jaundice.Light therapy which strikes the retina of the eyes is used to treat diabetic retinopathy and also circadian rhythm disorders such as delayed sleep phase disorder and can also be used to treat seasonal affective disorder, with some support for its use also with non-seasonal psychiatric disorders.Morningness–eveningness questionnaire
The morningness–eveningness questionnaire (MEQ) is a self-assessment questionnaire developed by researchers James A. Horne and Olov Östberg in 1976. Its main purpose is to measure whether a person's circadian rhythm (biological clock) produces peak alertness in the morning, in the evening, or in between. The original study showed that the subjective time of peak alertness correlates with the time of peak body temperature; morning types (early birds) have an earlier temperature peak than evening types (night owls), with intermediate types having temperature peaks between the morning and evening chronotype groups. The MEQ is widely used in psychological and medical research and has been professionally cited more than 3,000 times.Non-24-hour sleep–wake disorder
Non-24-hour sleep–wake disorder (Non-24 or N24SWD) is one of several chronic circadian rhythm sleep disorders (CRSDs). It is defined as a "chronic steady pattern comprising [...] daily delays in sleep onset and wake times in an individual living in society." Symptoms result when the non-entrained (free-running) endogenous circadian rhythm drifts out of alignment with the light/dark cycle in nature. Although this sleep disorder is more common in blind people, affecting up to 70% of the totally blinds, it can also affect sighted people. Non-24 may also be comorbid with Bipolar Disorder, Depression, and traumatic brain injury. The American Academy of Sleep Medicine (AASM) provides guidelines since 2007 with the latest update released in 2015.Photoperiodism
Photoperiodism is the physiological reaction of organisms to the length of day or night. It occurs in plants and animals. Photoperiodism can also be defined as the developmental responses of plants to the relative lengths of light and dark periods. They are classified under three groups according to the photoperiods: short-day plants, long-day plants, and day-neutral plants.Photoreceptor protein
Photoreceptor proteins are light-sensitive proteins involved in the sensing and response to light in a variety of organisms. Some examples are rhodopsin in the photoreceptor cells of the vertebrate retina, phytochrome in plants, and bacteriorhodopsin and bacteriophytochromes in some bacteria. They mediate light responses as varied as visual perception, phototropism and phototaxis, as well as responses to light-dark cycles such as circadian rhythm and other photoperiodisms including control of flowering times in plants and mating seasons in animals.Sleep diary
A sleep diary is a record of an individual's sleeping and waking times with related information, usually over a period of several weeks. It is self-reported or can be recorded by a care-giver.
The sleep diary, or sleep log, is a tool used by doctors and patients. It is a useful resource in the diagnosis and treatment of especially circadian rhythm sleep disorders, and in monitoring whether treatment of those and other sleep disorders is successful.
Sleep diaries may be used in conjunction with actigraphy.
In addition to being a useful tool for medical professionals in the diagnosis of sleep problems, a sleep diary can help make individuals more aware of the parameters affecting their sleep. This data alone can help people self-diagnose what helps them get a good sleep.Somnolence
Somnolence (alternatively "sleepiness" or "drowsiness") is a state of strong desire for sleep, or sleeping for unusually long periods (compare hypersomnia). It has distinct meanings and causes. It can refer to the usual state preceding falling asleep, the condition of being in a drowsy state due to circadian rhythm disorders, or a symptom of other health problems. It can be accompanied by lethargy, weakness, and lack of mental agility.Somnolence is often viewed as a symptom rather than a disorder by itself. However, the concept of somnolence recurring at certain times for certain reasons constitutes various disorders, such as excessive daytime sleepiness, shift work sleep disorder, and others; and there are medical codes for somnolence as viewed as a disorder.
Sleepiness can be dangerous when performing tasks that require constant concentration, such as driving a vehicle. When a person is sufficiently fatigued, microsleeps may be experienced. In individuals deprived of sleep, somnolence may spontaneously dissipate for short periods of time; this phenomenon is the second wind, and results from the normal cycling of the circadian rhythm interfering with the processes the body carries out to prepare itself to rest.
The word "somnolence" is derived from the Latin "somnus" meaning "sleep".Sundowning
Sundowning, or sundown syndrome, is a neurological phenomenon associated with increased confusion and restlessness in patients with delirium or some form of dementia. Most commonly associated with Alzheimer's disease, but also found in those with other forms of dementia, the term "sundowning" was coined due to the timing of the patient's confusion. For patients with sundowning syndrome, a multitude of behavioral problems begin to occur in the evening or while the sun is setting. Sundowning seems to occur more frequently during the middle stages of Alzheimer's disease and mixed dementia. Patients are generally able to understand that this behavioral pattern is abnormal. Sundowning seems to subside with the progression of a patient's dementia. Research shows that 20–45% of Alzheimer's patients will experience some sort of sundowning confusion.Suprachiasmatic nucleus
The suprachiasmatic nucleus or nuclei (SCN) is a tiny region of the brain in the hypothalamus, situated directly above the optic chiasm. It is responsible for controlling circadian rhythms. The neuronal and hormonal activities it generates regulate many different body functions in a 24-hour cycle, using around 20,000 neurons.The SCN interacts with many other regions of the brain. It contains several cell types and several different peptides (including vasopressin and vasoactive intestinal peptide) and neurotransmitters.Time shifting
As it relates to the circadian rhythm, timeshifting is the action of someone who is using individually timed light exposure and light avoidance, sleep and napping episodes, and/or melatonin use to adapt their circadian rhythm more quickly to a new sleep/wake and light/dark schedule in order to reduce jet lag or adapt to a new work schedule, or reset their circadian rhythm to ensure peak performance when needed, or in preparation for medical treatment.
In broadcasting, time shifting is the recording of programming to a storage medium to be viewed or listened to after the live broadcasting. Typically, this refers to TV programming but can also refer to radio shows via podcasts.
In recent years, the advent of the digital video recorder (DVR) has made time shifting easier, by using an electronic program guide (EPG) and recording shows onto a hard disk. Some DVRs have other possible time shifting methods, such as being able to start watching the recorded show from the beginning even if the recording is not yet complete. In the past, time shifting was done with a video cassette recorder (VCR) and its timer function, in which the VCR tunes into the appropriate station and records the show onto video tape.
Certain broadcasters transmit timeshifted versions of their channels, usually one hour in the future, to enable those without recording abilities to resolve conflicts and those with recording abilities more flexibility in scheduling conflicting recordings. (See timeshift channel.)