Here’s an overly simplistic explanation of sleep: it’s part of the circadian rhythm of life and is hardwired into the biology of persons and animals. Your brain wants to sleep when it gets dark and wake when it is light.
That’s partly true, but it’s not the whole story. A more precise explanation is that the sleep cycle stems from an interaction between the circadian clock and a separate sleep-wake homeostatic process. The "sleep homeostat" is, roughly, an accounting of the amount of sleep you’ve experienced recently. It causes the sleep drive to be based on how much sleep you’ve got in the past, and is directly related to the concept of sleep debt or sleep deficit. The sleep homeostat is similar to the hunger homeostat. If you haven’t eaten in a while, you’re likely to be hungry regardless of the time of day. If you had a feast at lunch, you may not be hungry come dinnertime. Likewise, if you’ve stayed awake all night, you’ll probably feel like sleeping in the morning, even if the Sun is up.
However, that’s not to say that the circadian cycle doesn’t matter. Cues such as daylight and regularly scheduled social and family activity have powerful influences on how sleepy or awake a person feels. These cues affect the internal clock.
Blind people often experience sleeping problems because their retinas are unable to detect light and they don’t have the circadian cues of daylight and night. Shift workers try to run their lives out of sync with light and dark cycles and consequently have problems.
To reduce the effects of jet lag, some therapists try to manipulate the biological clock with a technique called light therapy. They expose people to special lights, many times brighter than ordinary household light, for several hours near the time the subjects want to wake up. This helps them reset their biological clocks and adjust to a new time zone.
Disturbed circadian rhythms have been associated with a variety of mental and physical disorders and may negatively impact safety, performance, and productivity. Many adverse effects of disrupted circadian rhythmicity may be linked to disturbances in the sleep-wake cycle. Some rhythmic processes are more affected by the circadian clock than by the sleep-wake state, whereas other rhythms are more dependent on the sleep-wake state.
Circadian rhythms are ubiquitous in the animal kingdom, and are a cellular property. Neurons in a dish can act as clocks. The genes responsible for this cyclic behavior have begun to be identified. Clocks enable organisms to adapt to their surroundings. Although scientists currently believe that clocks arose through independent evolution and may use different clock proteins, they all share several regulatory characteristics. In particular, they are maintained by a biochemical process known as a negative feedback loop
Circadian Rhythms Nearly all physiological and behavioral functions in humans occur on a rhythmic basis, which in turn leads to dramatic diurnal rhythms in human performance capabilities. Regardless of whether it results from voluntary (e.g., shift work or rapid travel across time zones) or involuntary (e.g., illness or advanced age) circumstances, a disturbed circadian rhythmicity in humans has been associated with a variety of mental and physical disorders and may negatively impact safety, performance, and productivity. Many adverse effects of disrupted circadian rhythmicity may, in fact, be linked to disturbances in the sleep-wake cycle. Some rhythmic processes are more affected by the circadian clock than by the sleep-wake state, whereas other rhythms are more dependent on the sleep-wake state.
For most animals, the timing of sleep and wakefulness under natural conditions is in synchrony with the circadian control of the sleep cycle and all other circadian-controlled rhythms. Humans, however, have the unique ability to cognitively override their internal biological clock and its rhythmic outputs. When the sleep-wake cycle is out of phase with the rhythms that are con-trolled by the circadian clock (e.g., during shift work or rapid travel across time zones), adverse effects may ensue.
In addition to the sleep disturbances associated with jet lag or shift work, sleep disorders can occur for many other known and unknown reasons. And although disturbed sleep is a hallmark of many human mental and physiological disorders, notably affective disorders, it is often unclear whether the sleep disturbances contribute to or result from the illness. Other circadian rhythm abnormalities also are often associated with various disease states, although again the importance of these rhythm abnormalities in the development (i.e., etiology) of the disease remains unknown (Brunello et al. 2000).
One important factor contributing to researchers’ inability to precisely define the role of circadian abnormalities in various disease states may be the lack of knowledge of how circadian signals from the SCN are relayed to target tissues. To further elucidate the regulation of circadian rhythms, researchers need a better understanding of the nature of circadian signal output from the SCN and of how these output signals may be modified once they reach their target systems. Such an enhanced understanding also would allow for a better delineation of the importance of normal temporal organization for human health and disease. The finding that two major causes of death-heart attacks and strokes- show time-of-day variation in their occurrence is a case in point. If scientists knew more about the mechanisms responsible for the rhythmicity of these disorders, they might be able to identify more rational therapeutic strategies to influence these events. Finally, given that dramatic changes occur in the circadian clock system with advanced age, these changes may underlie, or at least exacerbate, the age-related deterioration in the physical and mental capabilities of older adults
How living organisms tune in to the time of day As any jet-setter knows, it takes time to adapt to the shifted day-night cycle of a foreign time zone. We have an internal circadian clock that times many physiological and behavioral events on a 24-hour cycle, according to day length. The clock can also reset itself, so we can cope with the seasonal variation in day light hours and the trappings of 20th century living such as shift work and air travel.
Not only humans have circadian rhythms. The eyes of marine mollusks, for example, show a correlation between perception of light and a circadian rhythm, as do the pineal glands of lizards and birds. The underlying clock that gives rise to these rhythms is dependent on feedback loops that regulate the expression of certain genes. Two animals in particular have given insight into the molecular mechanisms of internal clocks: the fungus Neurospora crassa and the fruit fly Drosophila melanogaster.
Several components of molecular clocks have now been cloned and sequenced. In Neurospora, the frq gene was the first found to be associated with period length; then two more genes, wc-1 and wc-2, were discovered in a strain of Neurospora that was blind to light. Both wc-1 and wc-2 are transcription factors that contain zinc fingers and transcriptional activation domains. Furthermore, these two proteins have PAS domains.
PAS domains were first identified in the Drosophila period clock protein PER, the vertebrate aryl hydrocarbon receptor nuclear translocator (ARNT), which is involved in a cell's response to lowered oxygen levels, and the Drosophila single-minded protein (SIM1), involved in the regulation of development. Many proteins have since been found to have PAS domains, which have now been shown to mediate protein-protein interactions.
A series of recent papers have confirmed that there is a common pattern to molecular clocks that has been conserved across evolution, from fungi to mammals. Part of the pattern is that PAS domains glue proteins such as wc-1 and wc-2 together to form a complex that switches on other clock components, such as frq, as a part of the organism's response to light. The frq protein then feeds back to inhibit the action of wc-1 and wc-2, thereby ultimately effecting its own expression. Signals from the environment, such as different light levels or temperature, could impact upon the loop to add more layers of regulation.
There are certain to be more feedback loops that are linked to this core component, because several observations have been made that do not quite fit this model, and it is not yet clear whether the clocks of plants or cyanobacteria will work in the same way. Perhaps these other cogs will be specific to different organisms, with only the "master clock", outlined here, being conserved across species.
Time will tell.
That’s partly true, but it’s not the whole story. A more precise explanation is that the sleep cycle stems from an interaction between the circadian clock and a separate sleep-wake homeostatic process. The "sleep homeostat" is, roughly, an accounting of the amount of sleep you’ve experienced recently. It causes the sleep drive to be based on how much sleep you’ve got in the past, and is directly related to the concept of sleep debt or sleep deficit. The sleep homeostat is similar to the hunger homeostat. If you haven’t eaten in a while, you’re likely to be hungry regardless of the time of day. If you had a feast at lunch, you may not be hungry come dinnertime. Likewise, if you’ve stayed awake all night, you’ll probably feel like sleeping in the morning, even if the Sun is up.
However, that’s not to say that the circadian cycle doesn’t matter. Cues such as daylight and regularly scheduled social and family activity have powerful influences on how sleepy or awake a person feels. These cues affect the internal clock.
Blind people often experience sleeping problems because their retinas are unable to detect light and they don’t have the circadian cues of daylight and night. Shift workers try to run their lives out of sync with light and dark cycles and consequently have problems.
To reduce the effects of jet lag, some therapists try to manipulate the biological clock with a technique called light therapy. They expose people to special lights, many times brighter than ordinary household light, for several hours near the time the subjects want to wake up. This helps them reset their biological clocks and adjust to a new time zone.
Disturbed circadian rhythms have been associated with a variety of mental and physical disorders and may negatively impact safety, performance, and productivity. Many adverse effects of disrupted circadian rhythmicity may be linked to disturbances in the sleep-wake cycle. Some rhythmic processes are more affected by the circadian clock than by the sleep-wake state, whereas other rhythms are more dependent on the sleep-wake state.
Circadian rhythms are ubiquitous in the animal kingdom, and are a cellular property. Neurons in a dish can act as clocks. The genes responsible for this cyclic behavior have begun to be identified. Clocks enable organisms to adapt to their surroundings. Although scientists currently believe that clocks arose through independent evolution and may use different clock proteins, they all share several regulatory characteristics. In particular, they are maintained by a biochemical process known as a negative feedback loop
Circadian Rhythms Nearly all physiological and behavioral functions in humans occur on a rhythmic basis, which in turn leads to dramatic diurnal rhythms in human performance capabilities. Regardless of whether it results from voluntary (e.g., shift work or rapid travel across time zones) or involuntary (e.g., illness or advanced age) circumstances, a disturbed circadian rhythmicity in humans has been associated with a variety of mental and physical disorders and may negatively impact safety, performance, and productivity. Many adverse effects of disrupted circadian rhythmicity may, in fact, be linked to disturbances in the sleep-wake cycle. Some rhythmic processes are more affected by the circadian clock than by the sleep-wake state, whereas other rhythms are more dependent on the sleep-wake state.
For most animals, the timing of sleep and wakefulness under natural conditions is in synchrony with the circadian control of the sleep cycle and all other circadian-controlled rhythms. Humans, however, have the unique ability to cognitively override their internal biological clock and its rhythmic outputs. When the sleep-wake cycle is out of phase with the rhythms that are con-trolled by the circadian clock (e.g., during shift work or rapid travel across time zones), adverse effects may ensue.
In addition to the sleep disturbances associated with jet lag or shift work, sleep disorders can occur for many other known and unknown reasons. And although disturbed sleep is a hallmark of many human mental and physiological disorders, notably affective disorders, it is often unclear whether the sleep disturbances contribute to or result from the illness. Other circadian rhythm abnormalities also are often associated with various disease states, although again the importance of these rhythm abnormalities in the development (i.e., etiology) of the disease remains unknown (Brunello et al. 2000).
One important factor contributing to researchers’ inability to precisely define the role of circadian abnormalities in various disease states may be the lack of knowledge of how circadian signals from the SCN are relayed to target tissues. To further elucidate the regulation of circadian rhythms, researchers need a better understanding of the nature of circadian signal output from the SCN and of how these output signals may be modified once they reach their target systems. Such an enhanced understanding also would allow for a better delineation of the importance of normal temporal organization for human health and disease. The finding that two major causes of death-heart attacks and strokes- show time-of-day variation in their occurrence is a case in point. If scientists knew more about the mechanisms responsible for the rhythmicity of these disorders, they might be able to identify more rational therapeutic strategies to influence these events. Finally, given that dramatic changes occur in the circadian clock system with advanced age, these changes may underlie, or at least exacerbate, the age-related deterioration in the physical and mental capabilities of older adults
How living organisms tune in to the time of day As any jet-setter knows, it takes time to adapt to the shifted day-night cycle of a foreign time zone. We have an internal circadian clock that times many physiological and behavioral events on a 24-hour cycle, according to day length. The clock can also reset itself, so we can cope with the seasonal variation in day light hours and the trappings of 20th century living such as shift work and air travel.
Not only humans have circadian rhythms. The eyes of marine mollusks, for example, show a correlation between perception of light and a circadian rhythm, as do the pineal glands of lizards and birds. The underlying clock that gives rise to these rhythms is dependent on feedback loops that regulate the expression of certain genes. Two animals in particular have given insight into the molecular mechanisms of internal clocks: the fungus Neurospora crassa and the fruit fly Drosophila melanogaster.
Several components of molecular clocks have now been cloned and sequenced. In Neurospora, the frq gene was the first found to be associated with period length; then two more genes, wc-1 and wc-2, were discovered in a strain of Neurospora that was blind to light. Both wc-1 and wc-2 are transcription factors that contain zinc fingers and transcriptional activation domains. Furthermore, these two proteins have PAS domains.
PAS domains were first identified in the Drosophila period clock protein PER, the vertebrate aryl hydrocarbon receptor nuclear translocator (ARNT), which is involved in a cell's response to lowered oxygen levels, and the Drosophila single-minded protein (SIM1), involved in the regulation of development. Many proteins have since been found to have PAS domains, which have now been shown to mediate protein-protein interactions.
A series of recent papers have confirmed that there is a common pattern to molecular clocks that has been conserved across evolution, from fungi to mammals. Part of the pattern is that PAS domains glue proteins such as wc-1 and wc-2 together to form a complex that switches on other clock components, such as frq, as a part of the organism's response to light. The frq protein then feeds back to inhibit the action of wc-1 and wc-2, thereby ultimately effecting its own expression. Signals from the environment, such as different light levels or temperature, could impact upon the loop to add more layers of regulation.
There are certain to be more feedback loops that are linked to this core component, because several observations have been made that do not quite fit this model, and it is not yet clear whether the clocks of plants or cyanobacteria will work in the same way. Perhaps these other cogs will be specific to different organisms, with only the "master clock", outlined here, being conserved across species.
Time will tell.