biological clock

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Self-sustained circadian (approximately 24-hour) rhythms regulating daily activities such as sleep and wakefulness were described as early as 1729. By the midtwentieth century it had become clear that the period of self-sustained (free-running) oscillations usually does not match that of the Earth's rotation (environmental cycle), therefore the expression “approximately 24 hours.” Moreover, the free-running period varies among species and also somewhat from one individual to another. Circadian rhythmicity is often referred to as the biological clock. See also Photoperiodism.

Almost all organisms display circadian rhythms, indicating an evolutionary benefit, most likely facilitating adaptation to the cyclic nature of the environment. Physiological processes that occur with a circadian rhythm range from conidiation (spore production) in the bread mold, Neurospora crassa, and leaf movements in plants to rest-activity behavior in animals. Despite the diversity of these phenomena, the basic properties of the rhythms are the same—they synchronize to environmental cues, predominantly light, but are maintained in the absence of such cues, and they display a constant periodicity over a wide temperature range.

In humans, circadian rhythmicity is manifested in the form of sleep-wake cycles, and control of body temperature, blood pressure, heart rate, and release of many endocrine hormones. It is increasingly apparent that temporal ordering is a fundamental aspect of physiological processes. In fact, several disorders such as asthma, stroke, and myocardial infarction also tend to occur more frequently at certain times of the day. Awareness of circadian control has led to the concept of chronotherapeutics, which advocates drug delivery timed to the host's circadian rhythms.

In mammals the “master clock” controlling circadian rhythms is located in the hypothalamus, within a small group of neurons called the suprachiasmatic nucleus. Available data suggest that the suprachiasmatic nucleus transmits signals in the form of humoral factors as well as neural connections. For many years the suprachiasmatic nucleus was thought to be the only site of a clock in mammals. This was in contrast to several other vertebrates where clocks were known to be present in the pineal gland and the eye as well. However, it is now clear that the mammalian eye also contains an oscillator (something that generates an approximately 24-h cycle) whose activity can be assayed by measuring melatonin release in isolated retinas. See also Nervous system (invertebrate); Nervous system (vertebrate).

The genetic basis of circadian rhythms was established through the identification of altered circadian patterns that were inherited. Such mutants were found first in Drosophila and then in Neurospora in the early 1970s. In addition, there is now an impetus to identify circadian abnormalities or naturally occurring variations in human populations. For instance, the difference between people that wake up and function most effectively in the early morning hours as opposed to those who prefer to sleep late into the morning may well lie in polymorphisms within clock genes.

It is now known that a feedback loop composed of cycling gene products that influence their own synthesis underlies overt rhythms in at least three organisms (Drosophila, Neurospora, and cyanobacteria) and most likely in a fourth (mammals). Similar feedback loops have also been found in plants, although it is not clear that they are part of the clock.

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Why do some of us have a harder time adjusting to jet lag or daylight savings time than others?

What about disruptions in sleep schedules? Our circadian (or biological) clock controls our bodies' sleep and wakefulness pattern, and that clock is regulated by DNA. On this date in 1994, an article was published in Science magazine announcing the discovery of a gene in mice which controls circadian rhythm; this was the first discovery of such a gene in mammals. Researchers continue to seek treatments for people who have trouble adjusting their biological clock.

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From our Archives: Today's Highlights, April 29, 2010

First recognized by the Chinese in the third century b.c.e., the biological clock is an intrinsic mechanism that controls the rhythm of various metabolic activities of plants and animals. Some, such as mating, hibernation, and migration, have a yearly cycle; others, such as ovulation and menstrual cycles of women, follow a lunar month. The majority, however, have a 24-hour, day-night cycle called the circadian rhythm. This day-night cycle, first recognized in plants over 250 years ago and existing in virtually all species of plants and animals, regulates these organisms' metabolic functions: plants opening and closing their petals or leaves, germination and flowering functions, changes in human body temperature, hormone secretion, blood sugar and blood pressure levels, and sleep cycles.

Research in chronobiology, the study of these daily rhythms, reveals that many accidents occur between 1 and 6 a.m., that most babies are born in the morning hours, that heart attacks tend to occur between 6 and 9 a.m., and that most Olympic records are broken in the late afternoon. The clock regulator may be the pineal gland located in the heads of animals (including humans).

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The innate rhythm of behavior and body activity in living things. A twenty-four-hour cycle of body activity, which operates in some organisms, is called the circadian rhythm.

Although the term biological clock refers to all innate timing mechanisms, it is often used when describing certain body functions that are subject to this rhythm, such as the loss of fertility with age.

Anybody who has crossed the Atlantic in an aeroplane knows about 'jet lag'. After a journey from London to New York it is difficult to stay awake, while after the return journey one tends to wake up late. Man's body is intolerant of changes in clock time and it takes several days to readjust to a new local time.

The same is true of practically all other animals, not very surprisingly, because we all live on the same planet and experience the same 24-hour cycle as the earth rotates. Mice, birds, and men eat and sleep at particular times of day, depending on their species, and if they are placed (or choose to place themselves) in unvarying habitats such as laboratories or down a mine they will generally retain these regular habits. The cycle tends to drift a little, with waking a few minutes earlier or later on each succeeding day, but it remains amazingly constant in duration. The rhythm of the body's activities can be reset by a new time of sunrise, or by a series of night shifts at a factory, but it cannot be substantially altered: man can be induced to live on a 23-or 25-hour cycle (by speeding up or slowing down his watch), but a 12-or 18-hour day seems impossible.

Shore-living invertebrates typically show an additional 'tidal' cycle, which has obvious adaptive significance, and many also show longer-term rhythms, coincident with the phases of the moon; species may spawn only at spring tides, or even only at spring tides at a particular time of year. Even annual rhythms may persist in constant conditions: weaver-birds, for instance, build nests and lay eggs at the 'correct' time of year for at least two years when deprived of day-length or temperature clues to the time of year.

There are also much shorter cycles — activities that are repeated every few seconds or minutes. Many sessile, burrowing, and boring animals lead monotonous lives in almost constant conditions and show these shorter rhythms very clearly. As with the circadian (circa diem, almost 24-hour) cycles, the rhythms tend to persist when all obvious sources of stimulation (even food) have been eliminated; they seem to be generated from within, rather than caused from outside.

The conclusion is that an animal contains one or more 'biological clock' (but the existence of several different rhythms in one animal does not necessarily imply several clocks — it could be a matter of gearing), and a great deal of research has gone into establishing the whereabouts of the mainsprings. A recurrent problem is that, because a body's various activities are interrelated, most if not all of its tissues operate to a cycle, and how does one distinguish between the mainspring and the rest of the clockwork? One approach is to determine which of the tissues will continue to perform rhythmically in isolation, although it is difficult to keep most tissues alive in a test tube, and even if one succeeds it is impossible to be certain that the tissue is behaving normally. The method is useful in the study of short-term cycles, however, and there are now a number of well-documented cases in which individual nerve cells have repeated regular patterns of electrical discharge over periods of hours or even days. The matter can be followed further into the cell, which may show cyclic changes in ribonucleic acid (RNA) content.

But where and how does the timing originate? Some argue that there is no endogenous clock and that the rhythms observed are driven from outside. It is impossible to disprove this, although in laboratories it is relatively easy to screen animals and plants (even potatoes show rhythmic cycles in respiration rates) from changes in lighting, temperature, and vibration. It is difficult, however, to screen them from daily changes in weak magnetic fields (and many are known to respond to these) and quite impossible to screen them from cyclic geophysical events such as the varying pull of the moon. Eventually the use of orbiting laboratories may help; in the meantime conventional wisdom holds that truly endogenous clocks are likely, even though it can offer no convincing models of how they may be engineered.

(Published 1987)

— Martin John Wells

Bibliography
• Moore-Ede, M. C., Sulzman, F. M., and Fuller, C. A. (1982). The Clocks that Time Us.

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any biological mechanism that allows the expression of a certain biological structure (e.g. a gene) or a biological function (e.g. sleep) at periodic intervals. The term is also used colloquially to describe ageing, e.g. in respect to a woman's ability to bear a child.

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For a list of words related to biological clock, see:

• Physiology - biological clock: internal factors that control innate body rhythms without external stimulation
• Pregnancy and Birth - biological clock: woman’s natural life cycle that controls ability to conceive and bear children

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