Circadian (Biological) Clock

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The word circadian was coined by biologists in the 20th Century, from circa, the Latin term for around, and diem for day. Other terms for biological rhythms are Ultradian, which are shorter term cycles and Infradian, which are longer than a day. Ultradian rhythms include eye blinking, heart beats, and breathing. Infradian rhythms are more evident in animals; the most prominent example in humans is the menstrual cycle.

Length of the Body’s Clock

Is the human circadian clock slightly longer than a day? It was long been thought to be about 25 hours in young adults, with the clock length shortening with age. That was the going theory for decades and explained why old people went to bed earlier and get up earlier than young people.

It is now felt that there is no significant difference in the circadian day with respect to age. Changes in the functioning of the suprachiasmatic nucleus (SCN) could be due to a disease rather than a normal consequence of aging. The ILP Workshop Report: Sleep, Health, and Aging cites polysomnographic work showing a decline in deep sleep (slow wave) from 18.9% of total sleep time during ages 16 to 25 to only 3.4% during midlife. Growth hormone levels also declined.

As humans progress from middle age to older ages, there is not a further decline in slow wave sleep. However, REM Sleep (stage R) decreases in late life and sleep fragmentation increases. The ILC Workshop Report claims “”the presence of disturbed sleep predicts overall health-related quality of life better than any other disease-activity measure in patients who suffer chronic illness.”

A decline in the power of the circadian cycle is common in older people and generally not welcome. The amplitudes of daily change decline with age. That is, the body doesn’t as readily vary from day to night. The body’s temperature, although it drops at night, does not drop as much as it does in younger people. The elderly brain does not release as much melatonin, which is why supplemental melatonin or melatonin agonists seem to be so effective in seniors. Retirement can remove many of the external social circadian cues. Having a routine reinforces circadian rhythms and helps many establish a regular sleep pattern. Decline in the vision system also play a part for many – cataracts reduce light signals hitting the retina, especially shorter waves in the visible spectrum which seem to be an important circadian cue.

This is why recommendations to seniors include intentional exposure to zeitgebers, which they might naturally get less of than young people.

The body secretes melatonin on cycle, independent of the homeostatic sleep drive. Bright light slows the release. In the temperate and arctic zones, daylight length changes over the course of the year. When days are long and nights are short (summer), the time of melatonin release is shorter. It is longer in the winter. Some animals appear to use the length of melatonin release in regulation of when life changes happen in accordance with the seasons. These include migration, mating, and molting.

Dozens, if not hundreds, of bodily functions are influenced by circadian cycles, not just sleep. One reason sleep emerges as such an important element in human flourishing is that it is part of the body’s overall integrity, encompassing so much and bringing so many sub-oscillators into line.

Every cell in the body has a small clock, in effect, an oscillator. The mechanism in each cell is not different significantly from the mechanism in the SCN pacemaker cells. The difference is that without signals from the SCN and elsewhere, the cell clocks fall out of sync.

Scientists have identified specific genes involved in the circadian cycle. These go by names like CRY, PER, CLOCK, and BMAL1. There are surely others that have yet to be discovered. The expression of these genes cycles throughout the 24-hour period.

The circadian cycles affect so many systems in the body that it is difficult to identify how they cause or influence disease or disorders. The circadian cycle is involved in many physiological processes, and it has even been shown that the likelihood of skin cancer developing after sunlight exposure depends on the time of day when the exposure occurs. There is a lot of mystery in this area, even to the top scientists, and much research needs to be done.

Circadian asynchonization affects so much in our experience of sleep. If we learn more details, we can perhaps make more progress in helping people sleep.

Biologists use the word phenotype to describe the way the genes play out in the environment that can be observed from the outside. There is no consensus here, but some consider the circadian cycle a phenotype and some consider chronotypes (e.g. morning lark, night owl) a phenotype or subphenotype.

Chronotypes can vary over the course of a person’s lifetime.

Researchers looking into chronobiology use behavioral signals to determine human chronotypes. Their initial classification is subjective and self-reported by the people under consideration. Subjects fill our surveys such as the Composite Scale of Morningness (CSM), the Munich Chronotype Questionnaire (MCTQ), and the Morningness-Eveningness Questionnaire (MEQ).

In some situations physiological evidence is obtained in the form of blood samples, thermometer readings, and other measurements, if required.

Across the Spectrum

Circadian rhythms have been found in living beings ranging from unicellular bacteria to higher mammals. Temporal orchestration of rhythmic protein activity and organelle function results in daily changes in the physiology of the organism. Most animals and plants have cycles tied to the sun. Some plants and animals in tidal regions have cycles that also correlate with the moon and tides.

Scientists have determined that the molecular timing mechanism (a.k.a. biological clock) works at the cellular level. Mammalian cells in a petri dish, separate from the rest of the animal, have a time cycle. Inside the cell, proteins are transcribed and translated in a feedback loop.

This cycle in turn regulates transcription of a large number
of genes. At the organism level, a master circadian oscillator in the brain’s hypothalamic suprachiasmatic nucleus (SCN) orchestrates tissue specific rhythmic activities. The SCN – in hypothalamus part of the brain – is a small (50k cells) area with big influence. Discovered in 1972 it functions as a master clock for the body.
The 2-process model of waking and sleeping proposes that the circadian cycle works in parallel with a homeostatic process of sleep desire build-up. More here.

In the early 20th Century scientists started seeing circadian patterns in animal behavior and showed that light-dark cycles affect the sleep patterns of mammals. In the 1930s the term “biological clock” was first used and in the 1960s it was shown that injuries to the hypothalamus area of the brain led to disruptions in the circadian cycle. Circadian cycles are still a major area of research for biologists and physiologists. More on different chronotypes.

Scientists produced mice without one of the genes important in circadian cycles, and the mice exhibited mania like that shown in individuals with bipolar disorder. The symptoms could be mitigated by giving the mice lithium. Aside from mental functions, circadian rhythms are involved in basic metabolic pathways. This is most dramatically demonstrated in deep sleep, when proteins are synthesized. Energy production at the biochemical level (glycolysis and fatty-acid breakdown) are also influenced by the circadian cycles.

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