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Aging

Aging

Aging is a physiological process of change that occurs in organisms over time. Indeed, in all cultures the aging of humans is the primary symbol for time’s passing. This entry focuses on the biological theories of aging and of the way in which the aging process affects human beings.

 

Theories of Aging

 

There are many theories that attempt to explain the cellular and molecular processes involved in aging. Some evidence appears to support the assumption that the aging of a given species is pro­grammed in some way. Monozygotic twins, for example, are much more likely to have nearly the same life span than are dizygotic twins. In labora­tory settings, the maximal life span of specimens is often similar. For example, the median life span of a housefly is around 30 days and of a rat approxi­mately 3 years. The maximum human life span is approximately 100 years, although in rare instances, individuals have lived as long as 115 years. In gen­eral it is possible to distinguish between systemic and genetic theories of aging.

Systemic theories propose that there is a systemic pacemaker for aging. One theory claims that the hypothalamus, a structure in the brain, has the function of a biological hourglass that begins to deteriorate in its hormonal output with the progress of time. This could lead to disorganization in the body’s homeostasis (balance of body functions).

A second theory is that the involution of the thy­mus, an immune system organ responsible for the imprint of T lymphocytes (T cells), leads to lower immunity. This could lead to more malignant pro­cesses in the human body.

Third, the autoimmune theory explains aging as an autoimmune process. Following this theory the body produces different antibodies against its own structures. These autoantibodies accumulate and lead to organ failures and dysfunctions.

Genetic theories are divided between damage and programmed theories. In contrast to systemic theories, they explain aging not by focusing on the organs, which work as an hourglass, but propose that aging happens in every cell of the human organism.

Damage theories of aging explain the process of aging by the accumulation of events damaging the genetic code of a cell. Oxygen radicals, which are developed in the metabolism of the cell, are being considered as one of the main mechanisms. Oxygen radicals damage the genetic code. Evidence for the relevance of oxygen radicals is given by the fact that the content of the enzyme superoxide dis­mutase, which catches free oxygen radicals, is pro­portional to the life span of different species. Cells of mice (life span 3 years), for example, have a low content of superoxide dismutase, gorillas (life span 55 years) a much higher one, and humans have one of the highest to be found in mammals. Other mechanisms discussed are oxidation, radiation, and glycation.

Theories of programmed aging conceive of aging as a process that is in some way programmed in the genetic code. The most famous among these theo­ries is the “length of telomere” theory. Telomeres are repetitive DNA sequences at the ends of chro­mosomes that stabilize the chromosomes. After every cell division, the telomere, which is about 2,000 base pairs long, is shortened by 50 base pairs. When a critical length is reached, the cell can­not divide itself any more and often dies by apop­tosis (programmed death of a cell). The telomere can also be elongated by the enzyme telomerase. Cells that express telomerase are factually immor­tal. In mammals this enzyme can be found only in cells of the germline, in stem cells, and in more than 90% of carcinomas. In Hutchinson-Gilford syn­drome (progeria) there is a genetic mutation that leads to faster shortening of the telomeres. People with this syndrome age far more rapidly than other people and die at the age of around 13 of stroke or cardiac infarction. Patients with this syndrome have atherosclerosis, osteoporosis, arthrosis, and aging of the skin, but other typical aging problems like dementia, hardness of hearing, diabetes melli- tus, and cataract are missing.

This leads to the observation that no single theory of aging is sufficient to explain all phe­nomena that occur in aging. The process has to be multifactorial.

Aging of the Human Organism 

It is possible to understand the word aging in two different senses. In the wider sense it deals with the whole human development; in the narrower sense it means the process of senescence, which under normal physiological conditions begins for most organs at about age 50. Death can of course occur at any phase of human development, but it occurs often the end of the described processes of aging. The physiological changes over time are the main physical characteristics of the passing of time for humans.

Three phases can be differentiated in the process of human aging. First, the embryonic phase from conception to birth; second, childhood (here under­stood to span the time from birth to the end of puberty); third, the time from sexual maturity to death. This differentiation is not fully sufficient if the focus lies on the organs.

The embryonic period begins with the fusion of the nuclei of sperm and ovum. After this moment the cell begins its development into a human being. After about 4 days of cell division, a trophoblast and an embryoblast are distinguishable. The first will develop to the organs of nutrition and implan­tation of the embryo, and the embryoblast will further differentiate itself to the fetus with func­tioning human organs. Between the 5th and 6th day the embryo implants in the mucosa of the uterus. The further differentiation takes place by three so-called blastoderms, which develop into the organ systems. This differentiation ends between the 8th and the 12th week of development. After this point all the organs exist, but they still have to run through a process of maturation until they are able to keep the newborn alive. Under natural con­ditions this point is reached around the 32nd week, although a normal pregnancy lasts 37 to 40 weeks. With intensive care it is possible for a newborn to survive from the 22nd week onward.

After birth the human development is character­ized by growth and maturation of the musculoskel­etal system and of most of the organs. The gonads start to grow during puberty (beginning between the 10th and 14th year); until then their size remains constant. After puberty the human skele­ton usually stops growing around the 18th to 22nd year. The process of senescence begins at different times in the different organ systems. In general there is a so-called organ reserve, which is the dif­ference between the maximal and the basal organ function. The basal organ function is sufficient to keep the organism working properly under physi­ological conditions. If there is a change in these conditions, the organ reserve is needed to compen­sate for these conditions. The cardiac output, for example, can be five times as high as the basal output. For most of the organs this organ reserve declines from the 30th life year onward.

The brain loses about 20,000 neurons per day from the 20th year on, a process finally leading to senescent atrophy of the brain. A symptom of this is a slight form of dementia, the benign senescent forgetfulness, which is physiological. Alzheimer’s disease is not regarded as physiological, as it involves the development of plaques that are deposited in the neurons, and results in an abnor­mally high loss of neurons. In lower amounts the plaques can also be found in the normal senescent brain. The dopaminergic system in the brain also degenerates, which leads to stiffer ambulation. Parkinson’s disease is another extreme form of a process of aging that can be found primarily in elderly people. In Parkinson’s disease the periph­eral nerves are demyelinating, meaning that their fatty covering or sheath slowly shrinks. This pro­cess leads to slower reactions. Other synthesizing activities of the brain are also deteriorating.

The endocrine system goes through different changes. In women the cyclical ovarial function terminates during menopause, usually between the 45th and 55th life year. Men, on the other hand, can have constant levels of testosterone from the 20th to 90th life year. In general the answer of organs to hormonal signals deteriorates, which may lead to illnesses. In the case of insulin, which is secreted by the pancreas, this process can lead to diabetes mellitus.

Presbycusis, with the difficulty of hearing high frequencies, is usually caused by degeneration of regions in the inner ear because of noise exposure during life. Decreased vision is most commonly a consequence of the reduced flexibility of the lenses although there are many other possible degenera­tions of the eye, such as in the vitreous body and the retina.

The lungs become less and less compliant, while the chest becomes stiffer and the cough reflex is reduced. These events lead to a lower level of oxy­gen in the blood and to an increased rate of respi­ratory infections.

In the cardiovascular system the arteries become stiffer because of atherosclerosis; this leads to higher blood pressure. The heart muscle fibers usu­ally become atrophic. Atherosclerosis of the coro­nary arteries can lead to disturbances of perfusion, which are followed by cellular necrosis.

With aging, the function of liver, kidneys, and gut is reduced. Like all other organs, these also become atrophic as a result of cells not being replaced after their physiological death. In general there is a lower amount of total body water and a higher amount of body fat. The connective tissue of the body is progressively reduced in its flexibil­ity from the 30th life year on. This leads to wrin­kles of the skin, which may be the most obvious sign of human aging.

 

Markus Peuckert

 

See also DNA; Dying and Death; Longevity; Medicine, History of; Senescence

 

Further Readings

 

Johnson, M. L. (Ed.). (2005). The Cambridge handbook of age and ageing. Cambridge, UK: Cambridge University Press.

Macieira-Coelho, A. (Ed.). (2003). Biology of aging. New York: Springer.

Sauvain-Dugerdil, C., Leridon, H., & Mascie-Taylor, N. (Eds.). (2006). Human clocks: The biocultural meanings of age. New York: Peter Lang.

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