Waterhouse et al. Journal of Physiological Anthropology 2012, 31:5
http://www.jphysiolanthropol.com/content/31/1/5

REVIEW

Open Access

Daily rhythms of the sleep-wake cycle
Jim Waterhouse1*, Yumi Fukuda2 and Takeshi Morita2
Abstract
The amount and timing of sleep and sleep architecture (sleep stages) are determined by several factors, importantamong which are the environment, circadian rhythms and time awake. Separating the roles played by thesefactors requires specific protocols, including the constant routine and altered sleep-wake schedules. Results fromsuch protocols have led to the discovery of the factors that determine the amounts and distribution of slow wave
and rapid eye movement sleep as well as to the development of models to determine the amount and timing of
sleep. One successful model postulates two processes. The first is process S, which is due to sleep pressure (andincreases with time awake) and is attributed to a ‘sleep homeostat’. Process S reverses during slow wave sleep(when it is called process S’). The second is process C, which shows a daily rhythm that is parallel to the rhythm ofcore temperature. Processes S and C combine approximately additively to determine the times of sleep onset andwaking. The model has proved useful in describing normal sleep in adults. Current work aims to identify thedetailed nature of processes S and C. The model can also be applied to circumstances when the sleep-wake cycle
is different from the norm in some way. These circumstances include: those who are poor sleepers or shortsleepers; the role an individual’s chronotype (a measure of how the timing of the individual’s preferred sleep-wakecycle compares with the average for a population); and changes in the sleep-wake cycle with age, particularly inadolescence and aging, since individuals tend to prefer to go to sleep later during adolescence and earlier in oldage. In all circumstances, the evidence that sleep times and architecture are altered and the possible causes ofthese changes (including altered S, S’ and C processes) are examined.
Keywords: Adolescence, chronotype, circadian rhythm, endogenous component, exogenous component, old age,
sleep homeostat, time awake

Review
Sleep in adults

Most adults take a consolidated 7-hour sleep during thenight [1]. The reasons for sleeping at night are partly
because the environment is quiet and also it would be
unconventional to arrange meetings or meet friends at
this time. Moreover, we are diurnal creatures and after anormal day when we have been awake and active forsome time, we feel tired in the evening and ready forsleep. It is possible to sleep at other times, as is evident
from the lifestyle of night workers but, even in a quiet
environment, daytime sleep tends to be more fragmented and shorter than nocturnal sleep. That is, the ability
to get to sleep and sleep uninterruptedly for longenough shows a daily rhythm. This rhythm of ease ofgetting to sleep (sleep propensity) is clear if individuals* Correspondence: waterhouseathome@hotmail.com
1
Research Institute for Sport and Exercise Physiology, Liverpool John Moores
University, Liverpool, UK
Full list of author information is available at the end of the article

miss a night’s sleep; they feel tired during the night but,in spite of having had no sleep, they then feel less tired
as the new day dawns and, during the afternoon, will
feel surprisingly alert. However, by the evening, the sensation of fatigue increases markedly and becomesincreasingly difficult to resist. This result indicates that
there is an increasing drive to sleep as the amount oftime awake continues to rise but that it is mixed with arhythmic component that varies during the course of
the 24 hours.
A good sleep is recuperative and removes the feelingsof fatigue (and also produces an improvement in cognitive ability); individuals then feel ready to face the rigors
of a new day. Intuitively, the concept of increasing ‘sleep
pressure’ with increasing time awake is not difficult toappreciate (even if the detailed nature of sleep pressure
is not understood). However, the presence of daily
rhythms in the desire to sleep, staying asleep and waking
up might be less easy to understand. In fact, when
repeated measurements are made over the course of© 2012 Waterhouse et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, andreproduction in any medium, provided the original work is properly cited.

Waterhouse et al. Journal of Physiological Anthropology 2012, 31:5
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24 hours in subjects who are living normally (active inthe daytime and sleeping at night), all physiological andbiochemical variables show daily rhythms. Some properties of such rhythmicity need to be considered, and they
will be illustrated by the rhythm of core temperature(which is representative of biological rhythms ingeneral).
Basic chronobiology
Endogenous and exogenous components of a rhythm

Figure 1 shows the 24-hour rhythm of core temperature
in a group of subjects living normally. The temperature
is higher in the daytime and lower at night. A priori, it
would be supposed that such rhythms result from thebehavioral changes that are associated with the sleepactivity cycle. During the daytime, individuals are physically and mentally active, and eat and drink in an environment that is busy and stimulating; all of these factors
will tend to raise core temperature. By contrast, atnight, individuals fast, are inactive, sleep and choose aquiet, dark environment.
In fact, such an explanation is only partially correct;
the standard method for demonstrating this is the ‘constant routine’. In this protocol, a subject is required toremain awake and sedentary (or lying down) and relaxed
for at least 24 hours in an environment of constant temperature, humidity and lighting; to engage in similar
activities, generally reading or listening to music; and to
take identical meals at regularly-spaced intervals. Such a
protocol removes any rhythmic changes due to the individual’s lifestyle or environment. When this protocol isundertaken, it is observed (Figure 1) that the rhythm ofcore temperature does not disappear, even though its

Figure 1 The daily rhythm of core temperature in a group ofeight young men. Full line: under normal conditions (sleep from
12 a.m. to 7 a.m., indicated by bar). Dashed line: undergoing a 24hour constant routine starting at 4 a.m. (From [2]).

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amplitude decreases. The rhythm shows a peak around
4 p.m. to 6 p.m. and a minimum around 4 a.m. to 5 a.
m. The rhythm is quite symmetrical, with the time ofmost rapid rise being in the period 7 a.m. to 10 a.m.
and that of most rapid fall around 10 a.m. to 1 a.m.
By considering the two temperature profiles shown in
Figure 1, the following deductions can be made [2,3]:(i) The rhythm observed during the constant routine
arises internally; it is the endogenous component of thetemperature rhythm and its generation is attributed to a‘body clock’.
(ii) Since the two rhythms are not identical, effects
due to the environment and lifestyle are also present
when the participants live conventionally; the difference
between the two rhythms is the exogenous componentof the rhythm. The exogenous component of core temperature is dominated by the sleep-wake cycle, activity
raising temperature and lying down and sleeping
decreasing it.
(iii) The two components are in phase. During thedaytime, body temperature is raised by the body clock
acting in synchrony with a more dynamic environment
and increased physical and mental activities; during thenight, the clock, a more restful environment and relaxed
lifestyle all act to reduce core temperature.
These deductions are general, insofar as all rhythms
show a mixture of endogenous and exogenous components when compared under normal living conditions
and during a constant routine. However, when different
rhythms are investigated, differences do exist, as
described below.
The origin of the exogenous component For example:
the exogenous component is the sleep-wake cycle in thecases of heart rate and blood pressure, as with therhythm of core temperature; it is the light-dark cycle formelatonin secretion; it is the rhythms of posture andfluid intake for urine flow; and it is the rhythm of foodintake for plasma insulin concentration.
The relative size of the endogenous and exogenous
components As Figure 1 indicates, these two components are of similar size for core temperature. By contrast, the exogenous component is larger than theendogenous component in the cases of heart rate, bloodpressure, urine flow and insulin secretion. For melatoninsecretion, provided light levels are low (as normallyfound domestically) - the exogenous component is smaller than the endogenous component. Because the relative sizes of the endogenous components of the rhythms
of core temperature and, particularly, melatonin aresmall, these rhythms are often used as ‘clock markers’.
The body clock and its adjustment by zeitgebers

The body clock consists of paired suprachiasmatic
nuclei at the base of the hypothalamus; many details of
its genetics and molecular biochemistry are now known

Waterhouse et al. Journal of Physiological Anthropology 2012, 31:5
http://www.jphysiolanthropol.com/content/31/1/5[4-6]. It is sited close to areas that exert widespread
effects upon the body (for example, temperature regulation, hormone secretion and the feeding cycle) andsends outflows to these areas, so producing rhythmicity
throughout the body.
When individuals are studied in time-free environments (such as an underground cave), the body clock
and rhythms produced by it continue to be manifest butwith a period closer to 25 than 24 hours. Such rhythms
are called circadian (Latin: about a day) and the timing
system is described as ‘free-running’. This period of
about 25 hours does not reflect the intrinsic period of
the body clock (tau) exactly, due to effects of light exposure during waking. Current evidence (from protocols
using very dim light during waking or from blind subjects) indicates that the true value of tau averages about
24.3 hours [7].
Whatever the exact value for tau in an individual, abody clock will be of value only if it and the rhythms it
drives are synchronized to a solar (24-hour) day. Thisadjustment is due to zeitgebers (German: time-giver),rhythms in the environment and/or the individual’s
behavior which show a 24-hour period. For humans, themost important zeitgebers are the light-dark cycle andrhythmic secretion of pineal melatonin during the dark.
Rhythms of physical activity, social factors and foodintake appear to play comparatively minor roles [8-10].
Nevertheless, whatever the details of the components ofa ‘zeitgeber package’, all potential zeitgebers normally
act harmoniously to adjust the body clock to the 24hour (solar) day.
The effect of light exposure upon the body clock
depends upon the time of exposure relative to the temperature minimum (normally around 4 a.m. to 5 a.m.,see Figure 1). Light exposure in the 6 hours after thisminimum advances the body clock to an earlier time, inthe 6 hours before the minimum, delays it, and at othertimes exerts no effect upon the clock [11]. Outdoor
light is more effective at adjusting the body clock thanis the dimmer light found indoors (that is, it tends to
produce larger phase shifts), even though domestic
lighting is normally adequate to act as a zeitgeber. The
relationship between the time when a zeitgeber is presented and the shift of the body clock that is produced
is called a phase-response curve.
Melatonin ingestion also adjusts the body clock; in theafternoon and early evening, melatonin ingestion
advances the clock and, in the second half of sleep andduring the early morning, delays it. Bright light inhibits
endogenous melatonin secretion, and the clock-shifting
effects of these two zeitgebers reinforce each other;bright light in the hours immediately after the temperature minimum advances the body clock directly via thephase-response curve (see above) and also indirectly (byPage 3 of 14

suppressing melatonin secretion and so preventing thephase-delaying effect that melatonin would have exerted
at this time) [12].
Sleep rhythms
Laboratory-based results

A laboratory environment is advantageous in that conditions conducive to sleep (quiet, comfort, and so on) can
be standardized. The standardization of such factors is
equivalent to standardizing the exogenous componentsof the rhythms of sleep. Studies in sleep laboratories
have systematically investigated the separate effects
upon sleep and sleep architecture (the distribution of
sleep stages) of time of day and time awake, which
together constitute the endogenous component of thesleep rhythms. Several protocols have been used, including the constant routine, multiple sleep latency tests andmodifying sleep-wake protocols (by changing the timeof day while maintaining time awake constant or changing the amount of time awake at the same times ofday). These protocols have been discussed in detail in
Reilly and Waterhouse [13]. Some of the main findings
from these investigations are detailed below.
Firstly, falling asleep is easiest if core temperature isfalling or low (evening and night) and most difficult if it
is high or rising (morning and afternoon). Secondly,
waking up spontaneously tends to be the opposite offalling asleep; it is easiest if core temperature is rising or
high, and most difficult when it is falling or low. These
last results explain why, if individuals have gone to bed
earlier or later than normal, even though they will feelless or more fatigued, respectively, than normal, they arelikely to have a longer or shorter sleeps, respectively,
than normal. Thirdly, the above two results stress thatthe ability to initiate and sustain sleep shows rhythmicchanges during the course of the 24-hour day, and thatthese are associated with the rhythm of core temperature. However, superimposed upon these effects is that
(if time-of-day effects are taken into account) sleep propensity - measured subjectively (fatigue, alertness) or
objectively (polysomnography) - increases in proportion
to time awake. This finding means that the endogenous
component of sleep rhythms, like those of alertness, fatigue and cognition, is a mixture of two main elements,
time of day and time awake. Finally, combining thesefindings indicates that an unbroken sleep is most likely
to occur if it starts in the late evening and ends sometime after 7 a.m., the individual having slept through thetrough of core temperature (see Figure 1). Sleep onset
will occur as core temperature falls, melatonin secretion
begins, fatigue increases and alertness falls, the individual having been awake for about 16 hours; sleep willend when core temperature rises and melatonin secretion falls.

Waterhouse et al. Journal of Physiological Anthropology 2012, 31:5
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Possible cause of rhythms of the sleep-wake cycle

The association between the sleep-wake cycle (sleep
propensity, sleep maintenance and waking up) and therhythm of core temperature has been interpreted as a
causal link, incorporating temperature-induced changes
in brain metabolism (see, for example, [14]). However,this might be an oversimplification of the position since
there are many other rhythms associated with the sleepwake rhythm [3,15]. These rhythms include: reciprocal
activity of the sympathetic and parasympathetic
branches of the autonomic nervous system (sympathetic
activity paralleling core temperature and parasympathetic activity showing a profile that is the mirror
image); levels of plasma adrenaline (parallel to core temperature); and plasma melatonin, concentrations ofwhich are low in daytime light, start to rise around 9 p.
m., peak during sleep in the dark, and fall on awakening
in the morning. Melatonin is known to cause cutaneous
vasodilatation (and so promote a fall of core temperature) as well as to increase fatigue. It is likely that manyfactors contribute to the physiological preparations thatneed to be accomplished to feel ready for sleep in theevening, to being able to maintain unbroken sleep atnight, to making preparations for waking up in themorning, and to being physically and mentally active inthe daytime. Core temperature is only one of these factors and should be seen as only one of the factors thatreflect the activity of the body clock and rhythmicity ofthe body as a whole.
The value of the rhythms of core temperature andmelatonin secretion as convenient markers of the timingof the body clock has already been mentioned. Alertness
and fatigue, important indicators of sleep-mediatedrecuperation and the need for sleep, respectively, arealso affected by the body clock. Once again, however,many other factors also contribute to these subjective
feelings (for example, boredom and excitement withtasks in hand and, particularly, time awake). The effects
of boredom and interest mean that alertness and fatigue
can be misleading indicators as to the physiologicalneed for sleep (the build-up of sleep pressure) at any
time. Even so, the principles involved in modeling therhythm of sleep times (see below) have also been used
to model rhythms of alertness, fatigue and mental activity (for details of which, see [16-20]).

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composition of successive cycles varies, with the amountof SWS decreasing and the amount of REM sleep
increasing.
Modeling sleep rhythms and the distribution of sleep
stagesThe basic model

One simple, and yet very effective, model of sleep
rhythms is the two-process model of sleep homeostasisof Borbély [21] (Figure 2). In this model, it is postulated
that one of the processes, sleep pressure (S), increases
during waking as an exponential saturating function,and then decreases exponentially during sleep (nowbeing termed S’). The other process, C, is rhythmic witha period of about 24 hours and consists of two parallel
components, an upper and lower component, both
approximately in phase with core temperature.
Sleep onset occurs when the rising value of S intercepts the upper C function, normally during the phaseof rapid decline and some hours before the minimum of
the upper C function. During sleep, the level of S’ falls
exponentially (but with a shorter half-time constant
than exists for S) until it meets the lower C function, at
which point waking occurs and the cycle starts again.
Waking normally occurs after about 7 hours of sleep, a
few hours after the minimum of the lower C function
when it is rising quickly. Factors S and C are assumed
to act additively (but see [22,23]).
A three-component model of sleep regulation, based
upon the two-component model but incorporating‘sleep inertia’, has been developed. Sleep inertia is the

Sleep

Wake

Sleep

Wake

Upper C

Sleep stages

Sleep is not homogeneous, and this has been investigated by recording surface electrical activity on the scalp
using an electroencephalogram (EEG). In normal sleep,
there is an ultradian rhythm of cycling between slow
wave sleep (SWS) and rapid-eye-movement (REM) sleep
stages, the REM-nonREM cycle. This cycle lasts
approximately 90 minutes, about five cycles occurring
during the course of a normal night’s sleep. The

Lower C

Figure 2 Times of sleep and wake (top, separated by the
double vertical lines). The C component is represented by two
curves (Upper C and Lower C). Sleep pressure increases
exponentially in the wake phase (Process S, dotted line) anddecreases at a faster exponential rate in the sleep phase (S’, dashedline). For more details, see text. (Based on [21]).

Waterhouse et al. Journal of Physiological Anthropology 2012, 31:5
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phenomenon whereby, immediately after waking fromsleep, the beneficial effects of sleep upon cognitive performance and mood are not immediately apparent[24-26].
Interpreting physiological and biochemical correlates of thesleep model

Many investigations have been performed to define
the physiological and biochemical correlates of processes S and S’ and the rhythmic function C, andothers are in progress. As with investigations of sleep
times, studies of processes S and S’ generally consistof measuring aspects of waking or sleep (subjective
estimates of fatigue and alertness, or objective measures of EEG during waking and sleep, for example)
after the sleep-wake schedules of volunteers have beenaltered in some way.
The general view (summarized in [22,27]) is that theamount of sleep pressure accumulated during the waketime (process S) is reflected in the amount of SWS that
occurs during the following sleep. Such ‘deep sleep’ hasbeen regarded for some time as the type of sleep thatbest reflects its recuperative role. The actual dissipationof sleep pressure (process S’) is associated with theamount of slow wave activity (SWA), assessed from thepower in the low-frequency band of the sleep EEG.
Increasing sleep pressure during the daytime when thesubject is awake can be measured by assessing sleep
propensity (the opposite of sleep latency) and the powerin the theta-alpha band of the waking EEG. Sleep pressure is also related to increasing subjective fatigue anddecreasing alertness. SWS and SWA are little affectedby core temperature; by contrast, the amount of REM
sleep is inversely proportional to core temperature andlittle affected by prior wake time. It is the difference
between the factors associated with SWS and REM
sleep that leads, during a normal nocturnal sleep, to thefirst REM-nonREM cycles being richer in SWS (beginning the process of recuperation) and the later ones,
closer to the temperature trough, richer in REM sleep.
However, the detailed nature of the links involved
remains unresolved. Comments already made aboutother variables being temporally associated with coretemperature (and, therefore, the C component), and allof them possibly being reflections of some more fundamental process, apply here also. The fundamental reasons why increased wake time leads to an increased
need for sleep and change in sleep architecture remain
to be elucidated. One approach to this problem has
been to investigate substances that accumulate in thebrain during the waking period and the neurophysiological changes that take place during this time [28]. However, detailed explanations of the associations between
sleep stages and time awake and core temperature arestill awaited.

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Using the two-component model to explain altered sleep
patterns in adults
Possible causes of differences in sleep patterns

With regard to adjustment of the body clock by zeitgebers, this process need not be precise on any particularday. Daily differences in detailed timing of biologicalrhythms will arise due to slight variations in the bodyclock and timing of the zeitgebers on a particular day.
Moreover, different individuals will show biological variation with regard to the exact intrinsic period of theirbody clock (tau), their exposure to zeitgebers and detailsof their phase-response curves to different zeitgebers.
That is, there will be both intra- and inter-individual
variation in the timing of the circadian clock and therhythms it drives.
Such variation will also apply when considering either
the sleep homeostat (S and S’) or rhythmic (C) components of the two-component model of sleep (Figure 2),
all of which is predicted to lead to changes in thedetailed timing of the sleep-wake cycle. Thus if the timing of the upper or lower components is changed, thiswill alter times of falling asleep or waking (times when
the S and S’ curves intercept the C curves); curves
phased earlier will tend to cause earlier times of sleep
onset and offset, and vice versa. If the amplitude of the
C rhythms is decreased, the angle between the S and C
curves will be less, and this will result in any changes in
the curves causing increased variations in the exact timing of the points of intersection; this will in turn cause
an increased variability in sleep onset and offset times.
If process S increases less with time awake (its half-time
constant is increased), then sleep onset will be delayed.
Finally, if process S’ is less marked (its half-time constant is increased), then sleep can be considered to beless recuperative (SWS and SWA will decline) and willtend to last longer.
These predicted changes can then form the basis ofattempts to explain some abnormalities of sleep behavior, even though the understanding is incomplete in
the absence of knowledge as to the exact correlates of
the S, S’ and C components (see above).
Adults who are poor sleepers and short-sleepers

Because, like any biological variable, the S, S’ and C
components will show inter- and intra-individual variation, there is the implication that the sleep-wake cycle
will differ between individuals and between days in asingle individual. It is common for individuals to delay
their sleep-wake cycle over the weekend (generally due
to increased social activities) and to find difficulty inreadjusting it to weekday requirements on the Monday.
There is also evidence that those with less regular lifestyles have more sleep problems [29]. These are external
factors, and so contribute to the exogenous componentof sleep rhythms, and readily modified by a change inWaterhouse et al. Journal of Physiological Anthropology 2012, 31:5
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lifestyle. The issue is if differences in the internal factors(S, S’ and C) are present in some cases of altered sleep.
There are differences in the amount of sleep habituallytaken by individuals because individuals choose to do
this (external factors), seem to need less sleep (’shortsleepers’), or get less sleep than they want and so feeltired in the daytime (’poor sleepers’). Studies using bedrest and sleep deprivation have been used to investigate
if poor sleepers show systematic differences from ‘normal’ sleepers [30], but they have not reliably shown thatthe sleep homeostat or rhythm of core temperature isdifferent. For example, the temperature rhythm andresponses to the multiple sleep latency tests following
these changed schedules were normal in poor sleepers.
Also, when short sleepers (< 6 hours per night) andlong sleepers (> 9 hours per night) were compared, both
responded in the same way with regard to the effect ofprior wake time upon the amount of SWS and the
kinetics of SWS during recovery sleep [31]. Therefore, it
has been suggested that short sleepers endure higher
sleep pressure, and that poor sleepers are not particularly susceptible to sleep pressure.
Even though these differences from normal sleep generally produce no more than some degree of inconvenience, they can be more troublesome if daytime fatigue ismarked and cognitive function impaired. In these cases,
treatment is sometimes contemplated, which generally
consists of attempts to strengthen the individual’s exposure to zeitgebers (particularly bright light) or regularingestion of melatonin a few hours before sleep isdesired [32-34]. In this regard, treatment is very similar
to that for aged subjects (see below).
The effect of chronotype

The measurement of a person’s chronotype score is now
commonplace, the original questionnaire having beentranslated into several languages (and then validated
upon local populations of subjects) and also adapted for
cultures that, for example, routinely rise early. A population’s chronotype scores are distributed normally, withthose who tend towards the ‘morningness’ part of the
distribution choosing to perform important activities in
the morning, and those tending towards ‘eveningness’choosing to do them in the evening. The tails of the distribution - the extreme morning types (larks) andextreme evening types (owls) - can find normal lifestyles
difficult to participate in fully and effectively. This difference might be due to habits (and so influence the times
of exposure to zeitgebers) and/or the body clock (tauvalues differing between individuals) and/or to the phase
response curves (which might differ in the size ofadvances and delays in the body clock that zeitgebers
produce), but few data on this issue are available. Whatcan be stated is that individuals are likely to have problems if they adopt an early lifestyle (retiring and rising

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earlier than average) but have a circadian system thattends to run later than average (for whatever reason), or
vice versa. Such disparities can be important for thoseworking shift systems.
The observation [35] that temperature rhythms inmorning- and evening-types during constant routines
are phased about 1 hour earlier or later than average,
respectively, implies that some endogenous component(differences in adjustment of the body clock? differences
in tau?) is involved, but it might also be caused partly
by the phase differences (due to different lifestyles) thatwere present in the days before the constant routine.
The S and C components of the two-process sleep
model have been compared in morning and evening
types, using the core temperature rhythm (a reflectionof the C component) and daytime measures of subjective sleepiness and alpha-theta activity (reflections of the
S component). The core temperature was phased earlier,and the build-up of sleepiness and alpha-theta activity
was more rapid, in the morning types; that is, both components of the two-component model were different[36]. In other studies, morning-types had more SWA at
the start of a recovery sleep following a night of sleep
disruption, and also showed a more rapid decay of SWA[37,38]. These results indicate that both processes S and
S’ might be more rapid in morning types, in addition toan earlier phasing of the body clock (see above), and all
factors might contribute to earlier times of retiring andrising.
There is evidence that some of the differences
between chronotypes and in processes S, S’ and C havea genetic basis. Evidence from a large study upon adults
in which sleepiness, chronotype, quality of life and sleep
times were compared [39] indicated that associations
existed that could not be explained by common lifestyles(those sharing the same household, for example); this
implies a genetic component. One of the clock genes,
PERIOD3, shows polymorphism and individuals homozygous for one variant, the five-repeat allele, PER3(5/5),
are not only more likely to be a morning type but also
more susceptible to the effects of sleep loss. By contrast,
individuals homozygous for another variant, PER3(4/4),
are more likely to be an evening type. Subjects homozygous for PER3(5/5) also showed more waking alphatheta activity, more SWA during sleep and a greater
decline in cognitive function when sleep-deprived [40].
A previous study [41] had also shown that individuals
could be divided into ‘resistant’ and ‘non-resistant’ on
the basis of deterioration of their brain function following sleep loss; since this division was independent of any
difference in phasing of core temperature, it seems torelate to the sleep homeostat rather than process C.
Two comparatively rare syndromes have been
described: delayed sleep phase syndrome and advanced

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sleep phase syndrome. In the former, the internal relationship between daily rhythms and the sleep-wakecycle is normal, except that the whole system is delayedwith regard to external time; for example, the core temperature rhythm shows a minimum around 8 a.m., andmelatonin secretion begins around midnight (bothrhythms being delayed about 4 hours compared withnormal). Subjects tend to wish to retire around 4 a.m.
and rise about noon, and this lifestyle can be very
inconvenient [42]. The opposite changes in timing ofdaily rhythms and chosen sleep-wake cycle apply toadvanced sleep phase syndrome. Behaviorally, the individuals can be considered as pathologically extreme examples of evening or morning types. Whether the
syndromes result from extreme values of tau, abnormal
phase-response curves, and/or abnormalities with regard
to the sleep homeostat is unknown.
In summary, evidence is beginning to be obtained thatindicates individuals’ chronotypes partly reflect some
aspects of the timing of their body clock and sleep
homeostat, and that a genetic component contributes tothese differences.
Differences in sleep patterns with age
Neonates and infants up to adolescence

Immediately after birth, neither full-term nor prematurebabies show clear circadian rhythms of the sleep-wakecycle or any other variable [43-45]. Instead, bouts ofsleep and waking alternate several times during thecourse of a 24-hour period. Therefore, the concept ofsleep pressure, accumulating with substantial periods ofwaking, cannot be applied in the same way. Further,
EEG results indicate that the nature of sleep is different,
there being two types of sleep, ‘quiet’ and ‘active’[46-48]. That is, the basic two-component model ofsleep cannot be applied to individuals in newborn
babies.
Even if the sleep-wake rhythm and other circadianrhythms developed progressively during the first years oflife, to become firmly established when the child is five
years of age [49-52], there are no studies in which components of the two-component model have been investigated in children of this age. The reasons for this areeasy to understand - requiring infants to take part insuch studies would be unethical.

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have access to television or live in latitudes where summer evenings can be very long) and so tend to be sleepdeprived on school days [53-64]. At weekends, they
catch up on lost sleep by extended time spent in bed(lie-ins). At the weekends also, the melatonin rhythm isphase delayed compared with during the week. Adolescents tend towards evening types, therefore, though thischange is more marked in some than others and occurs
at a slightly earlier age in girls, possibly due to their earlier onset of puberty [65]. The sleep restriction that is
experienced during weekdays causes concern withregard to school performance, particularly when school
starts early in the morning and the degree of eveningness of an individual is marked [66-71].
Some of these points are illustrated by some of ourunpublished data, which show changes in chronotype
and sleep quality in primary and secondary school students in Japan (7 to 18 years old; 404 boys, 411 girls).
The Japanese versions of Horne and Ostberg’s Morningness-Eveningness Questionnaire (MEQ) and the Pittsburgh Sleep Quality Index (PSQI) were used. Figure 3
shows the MEQ scores. Although most of the students
were neither morning type nor evening type, that is,they were ‘intermediate type’, the scores decreased significantly with age, indicating a change towards becoming evening type (boys: r = -0.99, P < 0.001; girls: r =-0.83, P = 0.041, Pearson’s correlation coefficients).
Female students older than 10 years tended to be more
evening types than their male counterparts, but this difference decreased with age and was reversed in students
aged18 years old. There was a clear linear relationshipbetween the MEQ scores and age of male students,
while this relationship was less clear in the female students and appeared to be affected other factors,

Adolescents

In practice, therefore, the earliest age at which substantial amounts of data have been collected is when thechild reaches adolescence, though here also experimental sleep-deprivation experiments have not been performed and no constant routine data are available. The
data that are available for this age group (10 to 17
years) are dominated by the observation that they go to
bed considerably later in the evening (particularly if they

Figure 3 Morningness-Eveningness Questionnaire (chronotype)scores in male and female school children of different ages.
Filled bars, boys; open bars, girls. Scores indicate: range 16 to 30,
definitely evening-type; 31 to41, moderately evening-type; 42 to 58,
neither or intermediate-type; 59 to 69, moderately morning-type;and 70 to 86, definitely morning-type.

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especially around 10 years of age. This change in female
MEQ scores at around 10 years might relate tomenarche.
Figure 4 shows that their PSQI scores tended toincrease significantly with age, indicating a deteriorationin sleep quality (boys: r = 0.96, P < 0.01; girls: r = 0.95,
P < 0.01, Pearson’s correlation coefficients), girls tending
to be worse than boys. Given that all students had torise at the same time in the morning to attend school,
the poorer sleep observed in the older children was consistent with the tendency for the chronotype in older
children to become progressively more orientatedtowards that of an evening type.
Attempts have been made to incorporate the findings
regarding lifestyle and chronotype in adolescents into
the two-component model of sleep regulation [72-74]. It
is believed that both components change. The evidence
for changes in the C component is the later phasing ofcore temperature and melatonin rhythms; the evidence
for a change in the sleep homeostat (S and S’ components) is an increase in sleep latency and a decline indelta power density. From a circadian viewpoint, thedelayed rhythms imply that early school hours will be
too soon after the trough of the core temperaturerhythm and time of high melatonin secretion (resulting
in poorer cognitive performance), and the fall in coretemperature and onset of melatonin secretion later inthe evening will delay sleep onset. The observed changes
in the sleep homeostat appear to enable these later bedtimes to occur.
Why such changes should exist during and just after
puberty is unclear; attributing them to the marked
maturational changes, in the brain as well as the pituitary-gonadal axis, is an obvious possibility, but details of
the mechanisms involved are unknown [75,76]. It is also
possible that the individual’s increasing independence atthis age means that personal interests might delay

Figure 4 Pittsburgh Sleep Quality Index scores in male andfemale school children of different ages. Filled bars, boys; open
bars, girls. Scores > 5 indicate some problems with sleep.

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bedtime, and this will lead to a delay in the circadiansystem. If this exogenous factor were important, thencurtailing evening activities and retiring earlier would
provide a suitable remedy; but if the driving force
behind the change were neurologically or hormonallybased (and internally-based), then advising earlier retiring times would be ineffective. Whatever the cause,
recommendations that school hours and examination
times should be delayed are common [66,68,70,71].
Older persons

There has been a large amount of research upon thesleep-wake cycle and associated rhythms in aged individuals, generally 55 years or older (for recent reviews, see[77-79]. Volunteers for such investigations have comefrom two main sources; those who come to the laboratory and those who live in homes for the elderly. The
type of person studied in these two cases might not be
the same. Subjects volunteering for laboratory-based
studies are likely to be healthy, active and independent;
those studied in homes are more likely to be less active
and independent, and also more likely to suffer fromsome of the problems associated with old age - forms ofdementia, for example. The concepts of ‘survivor’ and‘frailty’, respectively, have sometimes been used todescribe these two types of volunteer [80], and differences between the results given by them might be
expected.
Nevertheless, there are the following general findings[58,81-88]: daytime is associated with a greater numberof naps and night with greater sleep latency and more
fractionated sleep (sleep efficiency declines); theincreased frequency of waking is associated with a needto empty the bladder; and times of retiring and rising
tend to become slightly earlier, individuals become moreof a morning type. These changes to sleep and thesleep-wake cycle have been observed in longitudinal[89,90] as well as transverse studies, and made use ofmeasurements that have come from self-report diaries,
answering questionnaires, reports of care-givers or
objective measures of activity (by actimetry) or sleep(EEG and polysomnography).
Other factors that might be involved with changed
sleep-wake cycles are also found in aged individuals.
Poorer thermoregulation [91] and cognitive function[92] are present but, as in younger adults, a nap
improves cognitive performance [93]. Poorer sleep atnight and increased daytime naps will decrease the normal degree of dichotomy between daytime activity andnocturnal rest. Associated with this decrease is likely to
be decreased regularity of lifestyle and smaller exogenous components of circadian rhythms. Against this scenario, however, are the results from studies that haveshown an increase in lifestyle regularity [94-96]. Also,
following a simulated time-zone transition, aged

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persons, like younger adults, suffer from sleep loss anddeterioration in cognitive performance - but older subjects seem better able to pace themselves and maintaincognitive performance at times of sleep loss and low
core temperature [97,98]. There is also other evidence
that alertness in the aged seems to be less dependent
upon core temperature than is the case in younger subjects [99]. In other words, some of the behavioral
changes observed in aged subjects accord with the viewthat individuals try to adopt lifestyles that oppose thedifficulties that arise with aging.
Circadian rhythms alter with aging; those of core temperature and melatonin secretion having been studied
most. The amplitudes of these rhythms, when measured
in aged individuals living their normal lifestyles, normally show lower values when compared with younger
controls and phase advances in the order of 1 hour
[85,100]. There is also evidence that aged individuals
who suffer from poor sleep at night have a raised coretemperature at this time [101], but this is in contrast to
the results from an earlier study that had found thataltered sleep could not be accounted for by changed
rhythms of core temperature [102]. Such deteriorationin circadian rhythms is not observed equally in all aging
subjects [103,104] but tends to be more marked whenother problems (such as pain, failing cognitive powers
or senile dementia) are also present, and less marked if
a partner or companion is present.
Determining the cause of the observed changes is difficult because the links that exist between circadianrhythms and the sleep-wake cycle are complex. For
example, the need for recuperation during nocturnal
sleep might be lessened if, during the daytime, an individual is less physically and mentally active and takes
naps. Also, even though decreased activity of the suprachiasmatic nucleus (producing a rhythmic output that islower in amplitude) could account for many of theobserved changes, so too could, for example, decreased
exposure to or perception of zeitgebers, daytime activity
and exposure to the natural light-dark cycle being compromised by decreased mobility (not being able to venture outdoors) and/or poorer eyesight.
Poorer vision might be particularly important, causing
individuals to lack confidence and further restrict their
daytime activities, both indoors (reading, for example)
and outdoors (walking). The cornea and lens become
more opaque with age and light transmission, particularly of the shorter (bluer) wavelengths, decreases [105].
This acquired tritanomaly can be assessed objectively bya desaturated 15-hue test, in which patients are required
to distinguish between very similar shades of blue. Thispartial loss of perception of blue colors can also be seen
in some paintings in which, as the artist gets older,
there is more interest in reds and yellows than greens

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or blues. These changes in the perception of blue hues
can be marked in those who suffer from cataracts.
Light of shorter wavelengths is also important in thecontrol of body temperature, melatonin secretion andthe sleep-wake rhythm. Melatonin secretion in the lateevening and night promotes sleep, partly due to the fallin core temperature that it produces. This secretion issuppressed by light, particularly light at the blue end of
the visible spectrum [106-108]. Accordingly, it seems
possible that changing transmission of blue lightthrough the lens in aged subjects, particularly those suffering from cataracts, will change the pattern of melatonin secretion and times of sleep. For example, thedeclining transmission of blue wavelengths in the evening might lead to an earlier rise of melatonin secretionin the evening, contributing to earlier sleep onset inaged individuals. In addition, it has been observed [109]that daytime exposure to bright light in young adults
raises the secretion of melatonin at night, causes agreater fall of core temperature at this time, andimproves sleep; such effects might be less marked if thelens of the eye has reduced ability to transmit light atsome, or all, of the visible wavelengths.
Therefore, cataract surgery will not only improve individuals’ sight but it might also alter the quality of their
sleep. Asplund and Lindblad [110,111] found that a considerable proportion of the patients who had undergone
cataract surgery reported subjective improvements intheir sleep after surgery. This has recently been reexamined [112]. Fifteen patients were studied before andone month after cataract surgery, in which UV light-cutting intra-ocular lenses had been implanted. Vision andcolor perception both improved. After recovery fromthe surgery, they also demonstrated a change in nocturnal sleep, though this improvement varied between
patients. After surgery, patients showed a negative correlation between later wake-up or retiring times andsleep efficiency; that is, sleep efficiency of patients withearlier wake-up and retiring times was higher than inthose with later wake-up and retiring times. It seems
that, after surgery, the patients’ retinas received more
light of shorter wavelengths and this affected sleep
efficiency.
Whilst the detailed implications of these results withregard to the link between light perception and sleep
are still unclear, they do confirm that light, melatoninsecretion and sleep are linked. It is also noteworthy that,in aged individuals who do not suffer visual problems,
the phase shifts produced by exposure to bright light
are the same as in younger controls [113]. Also, a 3hour bout of exercise at the start of normal sleep timedelayed the melatonin rhythm equally in young and oldadults [114]. That is, there is no evidence that theincreased morningness found in aged individuals can beWaterhouse et al. Journal of Physiological Anthropology 2012, 31:5
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attributed to altered adjustment of the body clock byzeitgebers.
Attempts to interpret the causes of altered sleep patterns in the aged in terms of the two-component modelof sleep provide some evidence that both the C and S
components are altered, but interpretation of such
results is not without problems. For example, whilst
many circadian rhythms show decreased amplitude, thisdecline can be due to a fall in the endogenous or theexogenous component of the rhythm, or both. That is,
the observed fall in amplitude of the rhythm of coretemperature (which implies a change in the C component) might reflect decreased output from the suprachiasmatic nucleus (the endogenous component of therhythm), decreased secretion of melatonin (which causes
core temperature to fall due to cutaneous dilatation), ora decrease in the dichotomy between daytime activity
and nocturnal inactivity (the exogenous component).
Further, the tendency for aged individuals to become
more morning-orientated might be due to an alteredbody clock and/or timing of individuals’ lifestyles (factors that might reflect the C component of the twocomponent model in particular), or the more rapid
build-up of sleep pressure (the S component). A further
difficulty of interpretation arises because older individuals might go to bed earlier because their body clock is
running faster, their poorer eyesight restricts what they
can do (read or watch television), their declining mental
faculties mean they get bored more easily, sleep pressurebuilds up more quickly or they fear a poor sleep at nightand so want to attempt it sooner.
It is only the endogenous component of the rhythm ofcore temperature that is directly associated with component C. Since the endogenous and exogenous components of a circadian rhythm normally act together toproduce a measured rhythm, it is necessary to distinguish between them. The constant routine protocol isbelieved to enable the circadian output from the bodyclock to be assessed more directly. However, it must be
remembered that this protocol assumes that any effectsof the sleep-wake cycle upon the amplitude and phaseof the core temperature rhythm on normal days (whenthe exogenous component is present) do not continue
into the constant routine but disappear immediately it isundertaken. There is some evidence to support thisassumption, at least with regard to amplitude [115].
However, when aged participants undergo constant routines and their core temperature rhythm or secretion ofmelatonin in dim light is investigated (two common
markers of the body clock), there is evidence for a
reduced output from the body clock insofar as theamplitude of these rhythms is reduced; also, the temperature profile has been found to advance [116,117].
These results suggest the presence of a body clock with

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a declining output and an advanced timing. However,when the free-running period of the body clock was
examined in aged individuals who were blind (twice ineach individual, the occasions of study being separated
by a period of 10 years), where effects of light upon tau
are absent, the period lengthened [118]. Other studies
also have failed to find a consistent phase advance ofthe core temperature rhythm in sighted individuals
when using the constant routine protocol. Only an
advance of phase of the core temperature rhythm, possibly due to a reduction in tau, would indicate an endogenous cause for the increasing tendency tomorningness with aging (rather than an exogenous
cause such as preferring to get up earlier and go to bed
earlier). Therefore, the general position with regard to
the change in the endogenous component of the temperature rhythm in aged individuals is unclear. Again,
differences between survivors and the frail might beimportant.
The changes in sleep with aging might be explained interms of altered S and S’ processes. Investigations ofresponses to altered sleep-wake schedules (advancing ordelaying bedtime, for example) have shown that changes
similar to those found in younger adults under the same
circumstances are found for many sleep variables,
including sleep efficiency and time awake after sleep
onset [119]. The increase in sleep latency with age has
been taken to imply that sleep pressure decreases but,
again, contradictory results have been obtained. SWS
during the first part of a night’s sleep is normallydecreased in the aged [120,121]. The rate of dissipationof S (S’, as assessed from SWA) does not differ fromthat found in younger adults and, as in them, theamount of SWS increases following sleep-deprivation[122] and decreases in nocturnal sleeps taken after daytime naps [123]. On the other hand, another study
claimed that the relationship between SWS and priorwakefulness was different between aged participants andyounger controls [116] and that daytime naps led to afall in sleep efficiency and earlier waking [124]. Several
differences in the power of different frequency bands inthe EEG have been found in aged individuals comparedwith younger controls [120], though their detailed
meaning is unclear.
It has already been mentioned that those who seem toexperience fewer difficulties with sleep also seem tohave more regular lifestyles. It is stressed that thisincreased regularity might reflect a relatively stronger
output from the body clock (process C) or stronger
activity of the sleep homeostat (processes S and S’) - orit might be that increasing the exogenous components
of circadian rhythms, attempting to be active and so
promote accumulation of sleep pressure when awake,and having regular exposure to zeitgebers, can all beWaterhouse et al. Journal of Physiological Anthropology 2012, 31:5
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considered as ways of combating a declining influence ofendogenous components. Whatever the exact cause of
the decreased daily variability in some aged individuals,
it becomes translated into several ways of improving thequality of life of the aged, at least in those living inhomes for the elderly [125].
The general aim of these procedures is to increase thedichotomy between daytime activities in the light andnocturnal sleep in the dark [1,126-137]. Possibilities
include increasing daytime physical activity, outdoors innatural light, if possible and increasing daytime mental
activities, by providing an interest or getting individuals
to discuss topics of interest to them (their childhood,favorite food or films, for example). Increasing artificial
lighting levels is also used, not only to promote conditions suitable for taking part in activities but also to
inhibit napping. Coupled with these courses of action
can be encouragement to individuals to stay in bed atnight, even if they cannot sleep, with restricted use oflights (as long as requirements for safety and care aremet). In addition, some studies have indicated that theregular use of a mild soporific is effective (melatonin,for example), though the long-term use of any drug
requires medical advice [135,138,139].
Many of these treatments have been found to be effective; it often being stressed that individuals should be
encouraged to see some form of regular daytime activity
as a simple means of improving their quality of life. The
possible mechanisms which might cause the treatments
to be effective have been considered above; they mightact on the exogenous or endogenous component of circadian rhythms by promoting accumulation of sleep
pressure, and promote sleep pressure directly. Whichmechanism(s) are important is not yet known.
A rather different approach to the problem of improving sleep in older individuals is based upon the decline
in efficiency of thermoregulation with age [91]. Part ofthe problem is that, due to impaired cutaneous thermal
sensitivity, aged individuals are less able to perceive thetemperature of their surroundings, and so are unable toforestall falls or rises of body temperature by suitablebehavior. Additionally, sleep onset is inhibited by cold
hands and feet, and this is observed in all age groups.
Warming the feet by wearing bed-socks was found to
decrease sleep latency in aged individuals [140].

Conclusions
The two-process model of sleep has enabled the processes that determine sleep times and some aspects ofsleep architecture to be described. Equally, the constantroutine protocol remains the standard way of distinguishing between endogenous and exogenous components of circadian rhythms. Taken together, theseconcepts of a sleep homeostat and endogenous andPage 11 of 14

exogenous components of circadian rhythms haveenabled the quantity, timing and quality of sleep to beunderstood better. Such understanding has been applied
successfully to understanding the timing of sleep inhealthy individuals and in the changed circumstances ofadolescence and old age. However, details of the natureof the S, S’ and C components of the sleep model, andunraveling the interactions between these components
and those of the circadian rhythms, are still required.
Obtaining such details will improve our knowledge ofdifferences between healthy individuals at different
stages of their life-span and when suffering from somesleep disorders. Such deeper understanding will thengive a firmer rationale to advice and treatment, with thehope that they will become more successful.
Author details
1
Research Institute for Sport and Exercise Physiology, Liverpool John Moores
University, Liverpool, UK. 2Department of Living Environmental Science,
Fukuoka Women’s University, Japan.
Authors’ contributions
The preliminary draft of part of the section on adolescents was written by
YF, of part of the section on old persons by TM, and of the rest of thereview by JW. Thereafter, all authors were equally involved in the several
revisions that were undertaken. All authors read and approved the final
manuscript.
Competing interests
The authors declare that they have no competing interests.
Received: 8 February 2012 Accepted: 13 March 2012
Published: 13 March 2012
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doi:10.1186/1880-6805-31-5
Cite this article as: Waterhouse et al.: Daily rhythms of the sleep-wakecycle. Journal of Physiological Anthropology 2012 31:5.

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