What are biological clocks?

Types of Cycles

Biological clocks control a number of physiological functions, including sexual behavior and reproduction, hormonal levels, periods of activity and rest, body temperature, and other activities. In humans, phenomena such as jet lag and shift-work disorders are thought to result from disturbances to the innate biological clock.

The most widely studied cycles are circadian rhythms. These rhythms have been observed in a variety of animals, plants, and microorganisms and are involved in regulating both complex and simple behaviors. Typically, circadian rhythms are innate, self-sustaining, and have a cyclicity of nearly, but not quite, twenty-four hours. Normal temperature ranges do not alter them, but bursts of light or temperature can change the rhythms to periods of more or less than twenty-four hours. Circadian rhythms are apparent in the activities of many species, including humans, flying squirrels, and rattlesnakes. They are also seen to control feeding behavior in honeybees, song calling in crickets, and hatching of lizard eggs.

What is known about the nature of the biological clock? The suprachiasmatic nucleus (SCN) consists of a few thousand neurons or specialized nerve cells that are found at the base of the hypothalamus, the part of the brain that controls the nervous and endocrine systems. The SCN appears to play a major role in the regulation of circadian rhythms in mammals and affects cycles of sleep, activity, and reproduction. The seasonal rhythm in the SCN appears to be related to the development of seasonal depression and bulimia nervosa. Light therapy is effective in these disorders. Blind people, whose biological clocks may lack the entraining effects of light, often show free-running rhythms.

Genetic control of circadian rhythms is indicated by the findings of single-gene mutations that alter or abolish circadian rhythms in several organisms, including the fruit fly (
Drosophila melanogaster
) and the mouse. Some mutations in Drosophila produce shortened (nineteen-hour) or lengthened (twenty-nine-hour) cycles. The molecular genetics of each of these mutations is known.

A semidominant autosomal mutation, CLOCK, in the mouse produces a circadian rhythm one hour longer than normal. Mice that are homozygous (have two copies) for the CLOCK mutation develop twenty-seven- to twenty-eight-hour rhythms when initially placed in darkness and lose circadian rhythmicity completely after being in darkness for two weeks. No anatomical defects have been seen in association with the CLOCK mutation. In addition to the mouse, CLOCK is found in humans, Drosophila, and fungi, and is offset by the SIRT1 metabolic protein that regulates cells' energy use.

Biological Clocks and Aging

Genes present in the fertilized egg direct and organize life processes from conception until death. There are genes whose first effects may not be evident until middle age or later. Huntington’s disease (also known as Huntington’s chorea) is such a disorder. An individual who inherits this autosomal dominant gene is “programmed” around midlife to develop involuntary muscle movement and signs of mental deterioration. Progressive deterioration of body functions leads to death, usually within ten to thirty years. It is possible to test individuals early in life before symptoms appear, but such tests, when no treatment for the disease is available, are controversial.

Alzheimer’s disease (AD) is another disorder in which genes seem to program processes to occur after middle age. AD is a progressive, degenerative disease that results in a loss of cognitive function. Symptoms worsen until a person is no longer able to care for himself or herself, and death occurs on an average of eight to ten years after the onset of symptoms. AD may appear as early as the thirties or forties, although most people are sixty-five or older when they are diagnosed. Age and a family history of AD are clear risk factors. Gene mutations associated with AD have been found on human chromosomes 1, 14, 19, and 21; other candidate gene regions have been identified on chromosomes 2, 7, 9, 10, 11, 12, and 15. Although these genes, especially the apolipoprotein APOE ɛ4 allele, increase the likelihood of a person getting AD, the complex nature of the disorder is underscored when it is seen that some individuals with these mutations never get AD.

Impact and Applications

Evidence has accumulated that human activities are regulated by biological clocks. It has also become evident that many disorders and diseases, and even processes that are associated with aging, may be affected by abnormal clocks. As understanding of how genes control biological clocks develops, possibilities for improved therapy and prevention should emerge. It may even become possible to slow some of the harmful processes associated with normal aging.

Key Terms




Alzheimer’s disease


:

a disorder characterized by brain lesions leading to loss of memory, personality changes, and deterioration of higher mental functions





circadian rhythm


:

a cycle of behavior, approximately twenty-four hours long, that is expressed independent of environmental changes




free-running cycle

:

the rhythmic activity of an individual that operates in a constant environment





Huntington’s disease


:

an autosomal dominant genetic disorder characterized by loss of mental and motor functions in which symptoms typically do not appear until after age thirty




suprachiasmatic nucleus (SCN)

:

a cluster of several thousand nerve cells that contains a central clock mechanism that is active in the maintenance of circadian rhythms





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