Sleep Pressure and the Body Clock — One Hourglass, One Wall Clock

Two Things That Make Us Sleepy

A person who wakes up at seven in the morning and goes through the day will have heavy eyelids around eleven at night. Yet when that same person lands in a distant country by plane, they are often wide awake in the middle of the night there, even though they barely slept along the way.

These two scenes show that two things determine sleepiness. One is how long you have been awake, and the other is what time it is for your body right now. Sleep researchers believe these two interlock to determine when we sleep and when we wake up (PMID 15018264).

This article depicts the two as a pair of clocks. There is an hourglass where sand piles up while awake and empties while sleeping, and a wall clock that runs through the day whether sleeping or waking. The hourglass is in charge of how much sleep is needed, and the wall clock of the time the body guesses it is.

The Hourglass — Sleep Pressure That Builds Up the Longer You Are Awake

The person in the opening scene had been awake for sixteen hours by eleven o'clock at night. What accumulated during that time is one of the causes of sleepiness. Sleep pressure is the force that makes you want to sleep, which builds up the longer you stay awake and is released while you sleep.

This force is invisible, but it leaves traces in brain waves after you fall asleep. Large, slow brain waves appear in the sleeping brain, and their amount is determined by how much you slept beforehand and how long you have been awake (PMID 12700054). These large, slow brain waves are most abundant at the beginning of sleep and decrease as the night goes on, and the shape of that decrease in humans is steep at first and progressively gentler (PMID 35502706). Researchers use the amount of these brain waves as a gauge of sleep pressure (PMID 15018264). What kind of sleep these large, slow brain waves represent is covered in "Sleep Stages and Sleep Cycles".

Here, the hourglass is slightly different from a real hourglass. In a real hourglass, sand falls at a constant speed, but sleep pressure builds up quickly at first while you are awake and more slowly as it fills up, and even while you sleep, it is released quickly at first and then more slowly as time goes on (PMID 23899598). Therefore, the early part of sleep relieves the pressure the most.

The best-known candidate for the grains of sand is adenosine. Adenosine is a substance that acts as a signal in the brain to induce sleep. It is reported that this substance accumulates outside cells as nerve cells use energy while you are awake, and decreases while you recover during sleep. This change is particularly pronounced in a region at the lower front part of the brain (PMID 42059020). Research on adenosine encompasses both animals and humans (PMID 35575450). It is widely agreed that adenosine is a sleep-regulating substance produced by the body itself (PMID 35575450). However, the evidence that adenosine is directly involved in the regulation of sleep pressure is still under review, and questions that need answers remain regarding how precisely adenosine and caffeine regulate sleep (PMID 35575450).

The takeaway from the hourglass is one thing: the longer you stay awake, the more easily sleep comes, and when you sleep, that pressure is largely released starting from the front end.

Caffeine — Blocking the Receptor Sites

The way an afternoon cup of coffee pushes away drowsiness is also explained by adenosine. Adenosine attaches to the receptor sites on nerve cells to transmit signals (PMID 42059020). Caffeine attaches to those very sites instead, blocking adenosine's signals and thereby reducing sleepiness (PMID 35575450). People have regulated their sleep and wakefulness through this pathway for centuries (PMID 35575450).

What caffeine does is block the receptor sites. Reversing the pressure that has built up while awake is the job of sleep. To put it in terms of an hourglass, caffeine does not empty the accumulated sand; it covers it over so the weight of the sand is felt less. For the same reason, caffeine remaining in the body until bedtime can block sleepiness signals and make it difficult to fall asleep.

Whether the impact on sleep is the same when drinking caffeine once versus drinking it every day remains an open question (PMID 35575450). Other things that coffee does to the body are covered separately in "Coffee and Health — What We Got Wrong, and the Warnings That Still Hold".

The Wall Clock — A Day Inside the Body

Even when living in a place without windows or clocks, a person's body continues a rhythm roughly a day long. Making that rhythm is the second clock. The biological clock is a device inside the body that measures the time of day. The circadian rhythm is a roughly day-long cycle created by the body's internal clock, along which various bodily functions, including sleepiness and wakefulness, rise and fall. Not only sleep, but eating and various hormones also follow this cycle (PMID 36834801).

The center of the wall clock lies deep within the brain. The suprachiasmatic nucleus is a small cluster of neurons located right above the place where the nerves from both eyes cross over each other in the brain, serving as the central clock that leads the biological clock of the entire body. The suprachiasmatic nucleus receives light signals and aligns the clocks throughout the body, such as the liver and muscles, to its own time (PMID 41339276).

This wall clock turns by itself, but not at exactly twenty-four hours. The rhythm inside a person's body is very close to the length of a day (PMID 12828283), and light received mainly during the day tunes it to the exact day every day (PMID 36834801). Other signals, such as meal times, also have an effect, but the biggest signal that sets the clock is light (PMID 20308739). In the retina, there are cells used to see things as well as separate cells that detect light and inform the suprachiasmatic nucleus (PMID 38831000).

The role of light becomes apparent when light cannot reach the clock. In the most severe case, a person who has lost both eyes has the light signals from the retina to the clock cut off, so their biological clock detaches from the outside day and night and runs on its own. Then, symptoms similar to those after a long trip—sleepiness during the day, bad nighttime sleep, and mental fogginess while awake—can last a lifetime. For this condition, daily treatment with melatonin is used as a first-line therapy and has been reported to correct the clock's misalignment and improve sleep (PMID 17420154). Apart from setting the clock, light also plays a part in keeping the mind alert (PMID 29398582). The increased light received at night from smartphones, televisions, and indoor lighting is cited as a factor that disrupts the circadian rhythm (PMID 38160935).

The signal by which the wall clock informs the body of night is melatonin. Melatonin is a hormone produced in large amounts at night from a small gland deep inside the brain, signaling to the body that night has arrived. Blood melatonin is high at night and low during the day, and its secretion is controlled by the suprachiasmatic nucleus, which in turn is regulated by light (PMID 7803368). Bright light is the stimulus that most strongly suppresses melatonin secretion (PMID 15892931).

Melatonin is often thought of as a sleeping pill, but inside the body, melatonin provides feedback to the suprachiasmatic nucleus as a signal of darkness. Here, the action of inducing sleep and the action of aligning the sleep-wake rhythm work together (PMID 7803368). However, how much melatonin taken as a medicine helps with insomnia is a separate matter to be examined, and the judgment of guidelines is covered in "Insomnia and Sleep Apnea". The wall clock turns whether sleeping or awake, is tuned daily by light, and signals the night with melatonin.

Two Clocks That Together Decide Sleep

Putting an hourglass and a wall clock in the same picture is one of the most widely used frameworks in sleep science. The two-process model is an explanation that sleep pressure, which builds up the longer you stay awake, and a circadian rhythm that goes up and down over a 24-hour cycle mesh together to decide when you sleep and when you wake up. It was introduced over 40 years ago and is still used as a major framework in sleep science (PMID 35502706).

In this model, the wall clock sets two upper and lower thresholds for sleep pressure to move between (PMID 41775810). When the pressure reaches the upper threshold, you fall asleep, and when it is released during sleep and drops down to the lower threshold, you wake up. Because the height of those thresholds goes up and down depending on the time of day, even if you have been awake for the same amount of time, sleep may or may not come depending on the time. The model explains not only the time you fall asleep, but also the changes in how clear and foggy your mind is during the day, as the meshing of the two processes (PMID 15018264).

Let us follow the day around once. When you sleep enough and wake up in the morning, the hourglass is almost empty, and the wall clock points to morning. Sand piles up as much as you stay awake during the day. When night comes, the sand is piled high, and the wall clock raises melatonin to signal the night (PMID 7803368). At this time, when both clocks point toward sleep, sleep comes easily. Most of sleep and sleepiness is decided together by these two processes (PMID 31236513). Once you fall asleep, the sand empties quickly at first and slowly later (PMID 23899598).

A person pulling an all-nighter keeps piling up the sand without emptying it. The degree to which the mind gets foggy is worst around dawn, and may feel slightly better when morning comes. This is because the wall clock makes wakefulness and performance while awake go up and down along with sleep pressure (PMID 23899598). Still, the piled-up sand remains the same. What drops the day after pulling an all-nighter is covered in "Sleep Loss".

Whether the two clocks directly affect each other's operation is still not fully answered. While there is experimental evidence that the clock responds less to light when sleep pressure is high, evidence that the clock directly alters the operation of sleep pressure is scarce (PMID 31236513). Whether the two processes simply add together or are more complexly intertwined is also unresolved (PMID 12700054), and human experiments spanning 40 years have both results that fit the model and results that contradict it (PMID 42331996). Still, the picture to take away is simple. When you have been awake for a long time and your body clock points to night, sleep comes easily.

When the Clocks Are Out of Sync — Jet Lag and Shift Work

Let's return to our first traveler. Jet lag is the fatigue and sleep problem that occurs after rapidly crossing multiple time zones. The cause is that the body's internal rhythm does not match the day and night of the destination (PMID 11279722).

After arrival, the hourglass piles up as much as you stay awake at the destination. The wall clock still shows the time of the place you left. Even in the middle of the night at the destination, the wall clock may still show the daytime or early morning of the place you left. When the body's internal clock is out of sync with the outside day and night, excessive daytime sleepiness and nighttime insomnia appear (PMID 17118278). The wall clock moves to a new time while receiving the light of the destination (PMID 20308739).

Circadian rhythm sleep disorders is the grouped name for sleep disorders that occur when the sleeping time zone is out of sync with the outside day and night and the social day. Jet lag is one of them, and sleep disorders caused by shift work fall into the same group (PMID 18845459).

People who work night shifts experience a similar misalignment without travel. Both shift work and jet lag are situations where the body struggles to adapt to new time signals while sleep is not sufficient (PMID 31236513). Receiving light under lighting all night and having meal times shifted to the night disturbs the circadian rhythm (PMID 36834801). Because light is the biggest signal that sets the clock, night and rotating shift workers, along with the visually impaired, are prone to circadian rhythm sleep disorders (PMID 20308739). Shift work also appears alongside bodily illnesses. Gathering various studies targeting nurses, rotating shift work including night work was associated with gastrointestinal problems such as irritable bowel syndrome and diarrhea compared to day work, though most were observational studies surveyed at a single point in time (PMID 42326947). The possibility of an association between night work and the degree of arterial stiffness also appears, but it frequently became blurred when considering other factors like age together (PMID 42755473). Both are associations that appear together, and it has not been shown that shift work causes these illnesses.

The method of handling misalignment is also read through the two clocks. A 2009 clinical review lists using bright light and melatonin at appropriate times as the primary treatment for these sleep disorders. Because setting the time incorrectly can make things worse, the treating physician first asks about the patient's lifestyle in detail to gauge what time the patient's clock is reading (PMID 18845459). Since high sleep pressure makes the clock less responsive to light, there is also a proposal to relieve pressure with a nap so that the clock responds better to light (PMID 31236513).

The most prominent finding from the results of using melatonin for jet lag is that when you take it determines its effect. A 2001 review analyzing related trials showed that in nine out of ten trials, melatonin reduced jet lag. This was after flights crossing five or more time zones, and when taken close to bedtime at the destination. If taken incorrectly at an early time of day, even the same substance could cause drowsiness and actually delay adaptation to the destination time (PMID 11279722).

At the time in 2001, the authors concluded that melatonin has a clear effect in reducing jet lag, and that occasional, short-term use appears safe. Therefore, they wrote that it should be recommended for adult travelers crossing five or more time zones, especially eastward. The benefit was smaller for flights going west. They also noted points to watch out for. There were case reports that it could be harmful to people with epilepsy or taking warfarin, and they stated that pharmacological and toxicological studies of melatonin and product quality control are needed (PMID 11279722).

The reason taking time is so important is because melatonin is also a signal that signals night and sets the clock. The effect of melatonin varies depending on when it is taken, aligned with the time indicated by the person's clock (PMID 17420154, PMID 18845459). This part matches the clock-setting action we saw earlier (PMID 7803368). However, these results are about jet lag in travelers, not about sleepless nights in general. How guidelines view the use of melatonin for insomnia is covered in "Insomnia and Sleep Apnea".

Morning Types, Evening Types, and Teenagers Who Stay Up Late

Even under the same roof, there are people who wake up at the crack of dawn feeling refreshed and others whose brains only start turning on late at night. Chronotype is the individual difference in what time of day the body feels comfortable sleeping, waking, and being active, commonly divided into morning types and evening types. These individual differences in the circadian rhythm involve genetics and various other factors (PMID 23899598).

Chronotypes shift according to age. During adolescence, there is a substantial shift from a relatively morning type toward an evening type (PMID 23998671), while in older age, sleep timing tends to pull earlier, and when this becomes extreme enough to disrupt daily life, advanced sleep-phase disorder is also seen more often in older adults (PMID 20308739). Consistent observations accumulate showing that evening types lean toward worse outcomes across various aspects of well-being. Genetic, biological, developmental, and psychosocial explanations have been proposed together for why, and it has not yet been settled into one (PMID 31249496).

Entering the teens, sleep and wake times get later (PMID 17383934). This lateness is strongly intertwined with pubertal maturation (PMID 27450579). What causes this delay has not yet been settled into one, and explanations are largely split into two. The first is the wall-clock explanation. It states that during puberty, the biological clock's time itself is delayed, pushing back the sleep onset time (PMID 27546185). The second is the sleep pressure and lifestyle explanation. It states that the way sleep pressure builds up changes, and the amount and timing of light exposure change, causing people to sleep late and wake late. A review presenting this explanation considers that changes in clock period or light sensitivity alone are insufficient to fully explain this delay (PMID 27450579). A review combining animal data and two-process model calculations suggests that both sleep pressure and the biological clock, two processes, may be involved (PMID 23998671).

Sleep times get later, but when school starts remains the same, so sleep gets shorter. Teen sleep is characterized by being late and short, and insufficient sleep is linked to various functional declines in adolescents (PMID 32382399). Adolescence is a time of shifting toward eveningness, so that clock does not match societal demands such as early school start times (PMID 42480409).

When that mismatch is severe and long-lasting, it is treated as a medical condition. Delayed sleep-phase disorder is a persistent condition where one cannot fall asleep at the desired early time and finds it extremely hard to wake up in the morning. It is the most commonly diagnosed among circadian rhythm sleep disorders, is frequent in adolescents and young adults, and has much evidence relating it to a delayed biological clock. Treatments using medication, light, and behavioral therapy to advance the clock and sleep time are used and are effective at least in the short term, but follow-ups often show it shifting late again. Therefore, researchers think causes other than a delayed clock may also be at play (PMID 26434674).

Jet Lag Every Weekend

Consider someone who wakes up to an alarm on weekdays, and goes to sleep and wakes up two to three hours later on days off than on weekdays. Even without traveling, this person's sleep travels back and forth between two time zones two to three hours apart every week. Social jet lag is when the sleep schedules on weekdays and days off are misaligned, causing the body's internal clock and society's clock to not match. Shift work, late weekends, and early work and school start times create this mismatch (PMID 35659023).

Social jet lag is associated with depressive symptoms in young people aged 10–24, but the association was weak and varied greatly across studies. The association was clear when the difference between weekdays and days off was two hours or more, and was not clear when it was one to two hours. The authors noted that figuring out whether the relationship between the two is causal requires studies that follow the same people over a long period (PMID 40597088). There was also a small association with anxiety in adolescents aged 12–18, and the authors who pooled and analyzed these results emphasized that behavioral strategies targeting regular sleep are important for adolescent mental health (PMID 42480409). However, what this analysis pooled is a co-occurring association, and it did not test whether changing sleep regularly reduces anxiety.

Social jet lag is a small time difference that repeats every week. What it does to the body and mind is still being studied at the level of association. Whether sleeping in on weekends makes up for lost sleep is covered in "Sleep Loss".

Where to Look Next

Other parts of this series connect directly to this article. "Sleep Stages and Sleep Cycles" covers what kind of sleep the large, slow brain waves used in this article as a gauge of sleep pressure actually are. "Sleep Loss" covers the day after an all-nighter and the accumulation of short sleep, while "Insomnia and Sleep Apnea" addresses when sleep is disrupted by disease, including insomnia.

If you are curious about coffee itself beyond the story of adenosine that caffeine blocks, you can move on to "Coffee and Health — What We Got Wrong, and the Warnings That Still Hold", and if you are curious about what pushes back the sleep of teenagers who go to bed late, you can follow the sleep deprivation pathway in "Is Social Media Harming Adolescent Mental Health?".

Unresolved questions remain. Whether the hourglass and the wall clock directly alter each other's operation and what exact role adenosine plays in sleep pressure are still being studied.

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