The Biological Clock
The Biological Clock
A biological clock is a time-keeping system that ensures our ability
to adapt to and exist in harmony with the 24
night and seasonal changes of the earth. y generating 24 hour circadian
rhythms in our body for hormonal release and cardiovascular, behavioral and other
functions. The body contains several such clocks. B The Master "Biological Clock"(SCN)
In humans (and other mammals), it is housed in the brain's hypothalamus.
This is the master pacemaker
of our body's circadian timekeeping system.
The SCN consists of a pair of pinhead-size regions.
Each containing only about 10,000 neurons out of the brain's estimated 100
The SCN receives information about environmental lighting.
From the retina via optical
nerves and indirect pathways, thus . forming the main link between external
and internal times (There is also some evidence that the pineal gland
may be able to directly sense the light).
The SCN synchronises the peripheral clocks
throughout the body with external time, more or less on a 24 hr. cycle.
The emerging concept is that output signals from the master clock communicate
with peripheral clocks located in other areas:E.g. the brain, heart, lung, GI
tract, liver, kidney and fibroblasts - resulting in integrated circadian rhythms
for the body's physiological functions.
Via humoral pathways.
E.g. rhythmically released hormones like ACTH from the pituitary,
MELATONIN from the pineal, and corticoids (such
as CORTISOL) from the adrenals;
Via the autonomic nervous system
Via the regulation of activity, nutrient uptake
and core body temperature. E.g. SCN controls cycle/rhythm
of body temperature cycle. The temperature is lowest in the biological
night and rises in the biological daytime. This fluctuation persists even in
the absence of sleep. Activity during the day and sleep during the night reinforce
(entrain) this cycle of changes in body temperature.
The Circadian Rhythm
Almost every physiological variable in living (and developing)
organisms shows a circadian rhythm. Humans (and most vertebrates) have an
rhythm with a period of slightly more than 24 hours - i.e. a true circadian rhythm.
The existence of a circadian or daily rhythm is apparent in physiological,
pharmacological and pathological events - including:
Plasma levels of hormones.
E.g. MELATONIN, CALCITRIOL,
RENIN, ANGIOTENSIN, ALDOSTERONE, NOREPINEPHRINE,
INSULIN, PROLACTIN, GROWTH HORMONE, THYROTROPIN,
ATRIAL NATRIURETIC PEPTIDE, VASOPRESSIN;
Childbirth. In most women, natural
labor begins after midnight and delivery occurs around early morning.
Glattre and Bjerkedal, 1983 Cardiovascular function
Response to a glucose-tolerance test;
Performance variables - E.g. reaction
time, reading error, subjective alertness, working memory speed, self-chosen
work-rate; Birth and death rate;
Pharmacokinetics and effects of drugs;
Risk for cardio- and cerebrovascular attacks
Wever 1979, Reilly et al. 1997, Schwartz
1997, Lemmer 1999
The heart and circulation - E.g. cardiac output, heart rate, blood pressure;
The respiratory system - E.g. minute volume, oxygen consumption, carbon dioxide
The kidneys - E.g. glomerular filtration rate, urine flow rate, electrolyte excretion.
(Wever 1979, Reilly et al. 1997).
Premature babies exposed to cycled light grew
faster. Study involved 62 babies born at least 10 weeks prematurely
and weighing, on average, 2 pounds. They were randomly assigned to three groups
with different lighting conditions. It was found that
-at least 23 grams more per week -
than those who got cycled light near the end of their hospitalization. those exposed to
cycled light earlier grew faster
Brandon DH, Holditch-Davis D, Belyea M. Preterm infants born
at less than 31 weeks' gestation have improved growth in cycled light compared with
continuous near darkness. J Pediatr. 2002 Feb;140(2):192-9.
Circadian rhythms are of two general types
(1) Exogenous circadian rhythms.
Directly produced by an external influence, such as an environmental cue.
E.g. Light entering eyes. Since it is not generated by the organism itself, if the
environmental cues are removed, the rhythm ceases
(2) Endogenous circadian rhythms.
Driven by an internal, self-sustaining
biological clock rather than by anything external to the organism. E.g. cyclical
changes in core body temperature are endogenous. . They are maintained even
if environmental cues are removed
The endogenous circadian rhythm persists
in the absence of time cues, but can be entrained (synchronized)
to the 24-hour day:
Primarily by light / dark cycles.
Other factors involved in entrainment include:
Imposed behavior such as forced activity and
Social and nutritional feeding cues;
Knowledge of clock time;
Possibly electromagnetic fields;
The circadian rhythms vary for different species
at 8 am, temperature at 2pm and MELATONIN at
(E.g. rat). CORTICOSTERONE
peaks in the evening and temperature at night, whereas
MELATONIN matches humans.
Functions of the Biological clocks
The most important function of these clocks
is to regulate the biological rhythms in the 24 hour sleep/wake cycle:
Making you sleepy
at night /Awake during the day
night-time janitorial work on your immune system
Performing psychological balancing/reconciliation
activity. Equally important, but not well understood.
("Biological Clock") regulates MELATONIN
production and release into bloodstream
by being either ON or OFF - determined
by the presence of light or
darkness perceived by the eyes:
"Being OFF in the presence of
light the "Biological Clock" signals the pineal
gland NOT to produce MELATONIN.
By sending messages that block the pineal's
release of a chemical messenger, called NOREPINEPHRINE (NE) (from postganglionic
neurons from the superior cervical ganglia), which is needed for the pineal
to make MELATONIN. i.e. The
of the NE messenger ensures
that absence MELATONIN is not produced.
Being ON in
darkness the "Biological Clock" signals the pineal gland to produce
he presence of
messages via nerve connections from the eyes (the retinohypothalamic tract),
that has two concurrent effects: darkness
Instructs a group of cells (the superior
cervical ganglion) to make the chemical messenger
NE, but it can not be released until . . .
the "Biological Clock" to remove its blocking effect on the release of the chemical
messenger NE. Thereby permitting the pineal gland to produce
MELATONIN and secrete it into the bloodstream.
MELATONIN feeds back to the SCN to regulate its activity.
Most of the brain
receptors for MELATONIN
are located in the SCN (in mammals)
Can produce shifts in circadian rhythms in
a number of species. Including rats, sheep, lizards,
birds, and humans. Effects are most clearly evident when
MELATONIN is given in the absence of light
input. Thus, for example, giving MELATONIN
to blind people can help set their biological clocks.
Evidence that supplement
MELATONIN promotes sleep is inconclusive
Potential side effects of long-term administration
of MELATONIN remain unknown.
Its unsupervised use by the general public is discouraged.
Seasonal Rhythms. n addition to synchronizing daily rhythms, biological clocks can
affect rhythms that are longer than 24 hours, especially seasonal rhythms
Some vertebrate animals have reproductive systems
that can sense day length by the amount of MELATONIN
In hamsters. The
short days and long nights of winter turn off the reproductive systems
In sheep the opposite occurs.
The high levels of MELATONIN
that inhibit reproduction in hamsters stimulate the reproductive systems of
sheep, so they breed in winter and give birth in the spring. Body's Master clock (SCN) must be entrained to match environmental
The clock must be entrained, or reset, to
match the day length of the environmental
(i.e. day/night) light /
dark Because the circadian clock in most humans has a natural, inherent day length
, just over 24 hours
The cue that synchronizes the internal biological
clock to the environmental cycle is
in the retina transmit light-dependent signals to the SCN. Interestingly, our usual
visual system receptors, the rods and cones, are apparently not required for this
photoreception. Special types of retinal ganglion cells are photoreceptive, project
directly to the SCN, and appear to have all the properties required to provide the
light signals for synchronizing the master clock. At the SCN, the signal interacts
with several genes that serve as "pacemakers." Photoreceptors
Diagram shows a day-by-day representation of one individual's
The dark gray
periods of sleep, and the light gray
periods of being awake
Days 1-9 represents this individual's normal sleep/wake
cycle. Under these conditions, .
the individual is
exposed to regularly timed exposure to alternating daylight and darkness, which
has entrained this person's sleep/wake cycling to a period of 24 hours
Days 10-34 this individual has been isolated from
normal environmental cues like daylight, darkness, temperature variation, and noise
This individual's sleep/wake cycle continues
to oscillate in the absence of external cues, showing that this rhythm is endogenous,
or built in.
In the absence of external cues to entrain
circadian rhythms, this individual's clock cycles with its own natural, built-in
rhythm (just over 24 hours long) - Consequently, without environmental cues,
the individual goes to bed about one hour later each night. After 24 days, the individual
is once again going to bed at midnight, . the time to which the SCN was previously
from the inability of our circadian clock to make an immediate adjustment to the
changes in light cues that an individual experiences when rapidly crossing time
zones. After such travel, the body is in conflict. The biological clock carries
the rhythm entrained by the original time zone, even though the clock is out of
step with the cues in the new time zone. This conflict between external and internal
clocks and signals is called Jet lag. R desynchronization .
Note that ALL the body rhythms are out of
sync. Affects more than just the sleep/wake cycle, and they
. take a number of days to re-entrain to the new time zone
Eastward travel generally causes more severe
jet lag than westward travel. Because traveling east requires
that we shorten our day and adjust to time cues occurring earlier than our clock
is used to.
The 20th century saw the recognition that all living beings, including
unicellular organisms, possess a biological clock system that measures time
in near 24-h (circadian) units resulting in rhythmic patterns with a period
of 24-h, termed circadian rhythms. The tendency of some organisms to sleep
at night and some during the day, and the fact that some plants open their
leaves during the day and close them at night, are common observations.
The reasonable assumption that these are passive responses to the day/night
changes in the environment was proven wrong by a simple yet brilliant experiment
performed in the 18th century. In 1729, French astronomer Jean Jacques d'Ortous
de Mairan showed that the upright movement of the leaves of the plant Mimosa
pudica at nighttime and the opening of these leaves during the daytime hours
continued over several days when the plant was maintained in constant darkness,
indicating that the leaves' movement followed an endogenous 24-h clock.
Moore-Ede et al., 1982