biological rhythms

biological rhythms Life has evolved in a rhythmic environment. For example, the daily rising and setting of the sun, and the seasonal variations in day length, temperature, and rainfall are all major factors to which the physiology and behaviour of different species must adapt in order to survive. The most obvious manifestation of human rhythmicity is the cycle of sleeping and waking. Humans are diurnal creatures; that is to say we are active during the light phase of the day and sleep at night. Anyone who has kept a pet hamster will know that these and many other species are nocturnal, i.e. active at night. But whilst the sleep–wake rhythm is obvious, virtually all the rest of our functions have their own, less evident rhythms. In fact it would be reasonable to say that everything that happens in our bodies is rhythmic until proved otherwise.

Many different frequencies are present in biological rhythms apart from the sleep wake (a 24-hour rhythm) and seasonal variations. The human pulse rate, at around 72 beats per minute, and the firing of nerve fibres (usually at rates up to hundred per second) are examples of rhythms with high frequencies. Population variations (most evident in sub-human species) are examples of low-frequency rhythms. The menstrual cycle of 28 days has been associated with the lunar cycle, but there is no proof of a definite link.

We know most about our 24-hour rhythms. It would be reasonable to assume that the setting of the sun or the extinction of artificial lights at night, perhaps combined with social conditioning to go to bed in the evening, makes us sleep. These certainly play a role, but the most important factors determining the timing (and structure) of sleep are an internal drive to sleepiness (the biological clock) together with accumulated tiredness since the last sleep. Many years ago, experiments in deep caves and in ‘temporal isolation’ units showed that, in the complete absence of any known time cues such as changes in the light level and ambient temperature, with no knowledge of clock time, radio, TV, newspapers, telephone, or contact with other people, humans still continue to live on an approximately 24-hour day. This observation is taken as evidence for the existence of an internal rhythm generating system of approximately 24 hours, which has come to be known as the biological clock.

Most people in such a time-free environment get up a little later and go to bed a little later each day: their personal in-built periodicity is slightly longer than 24 hours. The average period of the human body clock was thought to be 24.9 hours, but has recently been revised to be about 24.2 hours, on average. This natural rhythm, close to but not exactly 24 hours long, is called a circadian (meaning ‘about a day’) rhythm. A very few people have a periodicity shorter than 24 hours. Periodicity appears to be an inherited characteristic. Together with the sleep rhythm, many other major body functions exhibit circadian rhythms, including: secretion of hormones (e.g. the ‘darkness’ hormone melatonin, usually high at night, and the stress hormone cortisol, usually high in the morning); the production of urine and the variation in deep body temperature (usually low at night); the biochemical composition of the blood; alertness; and the ability to perform cognitive and dextrous tasks. Examples of rhythms that are not internally generated include the salivation and insulin responses to periodic meals.

Endogenous rhythms predict and prepare our bodies for forthcoming events: increased sleepiness in the evening prepares us for sleep, increased deep body temperature in the morning heralds wake-up. Some of the most striking examples of predictive rhythms are seasonal breeding patterns in long-lived animals. Sheep mate in the autumn and give birth in the spring — a time of year most propitious for survival of the lambs. These events are dictated by an endogenous seasonal rhythm of reproductive competence.

Since endogenous rhythms do not have exactly the same periodicity as the corresponding environmental cycle, they have to be reset by external time cues. The most potent of the signals for circadian synchronization, in the vast majority of species, including humans, is the daily light–dark cycle. The annual change in day length is the primary cue for timing seasonal cycles in most species. An inherent rhythm that is delayed a little each day (such as the natural human circadian clock of some 24.2 hours) must obviously be advanced each day (by 0.2 hours) to stay locked to the outside world. Exposure to bright light in the early morning, shortly after the deep-body temperature reaches its minimum value, will advance the circadian rhythm, while similar exposure to light in the late evening, before the temperature minimum, will delay it. Social interactions, mealtimes, exercise, and knowledge of clock time all help to keep us synchronized.

The major internal rhythm-generating system of mammals is found within the brain, in a pair of tiny structures known as the suprachiasmatic nuclei (SCN). Each SCN is a group of a few thousand nerve cells, sited in the hypothalamus, just above the optic chiasma (the crossing of the optic nerves). Destruction of this small area in rodents abolishes nearly all circadian rhythms, although there is a supplementary ‘clock’ in the retina itself (at least in hamsters). Amazingly, transplantation of the SCN from one hamster to another in which it has been damaged restores rhythmicity (of activity–rest) to the host animal, and confers on it the natural periodicity of the donor animal. It is assumed that the same would be true of humans. A small number of nerve fibres branch off from the optic nerve into the SCN. The information they carry enables the mammalian circadian rhythm generated in the SCN to be reset by light.

In most lower vertebrates, both the retina of the eye and the pineal gland in the brain are also capable of generating circadian rhythms. All rhythm-generating tissues (SCN, retina, pineal gland) show circadian rhythms of physiological activity even if they are removed and maintained, alive but isolated, in a cell culture chamber (a clock in a dish). Nerve cells of the SCN fire impulses in extremely regular patterns, like metronomes, and the frequency of the pattern varies with the time of day; cells of the retina and the pineal gland secrete the hormone melatonin in amounts that vary with the time of day. Each rhythm-generating cell contains a self-sustaining ‘oscillator’. In the case of the retina and the pineal of lower vertebrates, the cells involved are direct photoreceptors. In some non-mammalian vertebrates the pineal gland appears to be the master clock. In the sparrow, Passer domesticus, for example, removal of the pineal gland leads to loss of the activity–rest rhythm, and transplantation of a pineal from another bird not only restores rhythmicity but confers the phase of the donor to the host.

The hormone melatonin is the main output of the ‘clock’ of most vertebrates so far investigated. In mammals, where the SCN is the major clock, melatonin is synthesized mostly in the pineal gland under the control of the SCN. It is normally made at night (or during the dark phase). Light serves both to synchronize the rhythm to 24 hours and to regulate the duration of night-time secretion: in winter (long nights) the secretion profile is longer than in summer (short nights). It is this changing duration of melatonin (the darkness hormone) that acts as a time cue for the organization of seasonal physiology in photoperiodic mammals (those that depend on daylength to time their seasonal functions). The role of melatonin in circadian organization is very important in those species that use the pineal and/or the retina as a clock. In mammals (humans and rodents) it has only modulatory effects on circadian rhythms. It probably serves to reinforce and elicit physiology and behaviour associated with darkness. And it can also act on the SCN itself, producing ‘feedback’ resetting of the clock.

The real importance of the biological clock is evident when things go wrong. Disturbed rhythms are found in blindness, shiftwork, jetlag, certain insomnias, some psychiatric conditions and in some elderly people. Blind people with no conscious (or even unconscious) light perception lack the external light–dark changes that normally reset the body clock each day, and hence many have problems living on a 24-hour day. They manifest their own, endogenous periodicity, which means that, every few days or weeks, when their own clock has drifted out of phase with the world, they go through periods of feeling extremely sleepy and/or napping during the day, and being wide awake at night. Night shift workers are usually unadapted: they are therefore trying to work at the lowest ebb of their alertness and performance rhythms, and have problems sleeping, out of phase, during the day. This is the probable explanation for the increase in accidents on night shifts and for the many health problems of shift workers. A similar problem occurs for people travelling quickly over many time zones (jet lag): the clock adapts only slowly to such abrupt changes of phase. There are moreover a number of other conditions of clock dysfunction, such as delayed and advanced sleep-phase syndrome, and possibly a general lack of robustness of rhythms in some elderly people.

It is reasonable to assume that improper functioning of the circadian system is deleterious to health. Since bright natural light is more effective at synchronizing rhythms than domestic intensity light, urban populations (who generally live in a relatively light-deprived environment) are most at risk. Both bright artificial light and administration of melatonin at night time can be used to reinforce circadian organization and to hasten adaptation to phase shifts, for instance as a remedy for jet lag. At present there is considerable interest among pharmaceutical companies in the development of artificial analogues of melatonin.

Josephine Arendt

Bibliography

Arendt J. (1995). Melatonin and the mammalian pineal gland. Chapman Hall, London, New York.
Miller, J. D.,, Morin, I. P.,, Schwartz, W. J., and and Moore, R. Y. (1996). New insights into the mammalian circadian clock. Sleep 8 641–67.