Why Study Aging? (Genetics & Inherited Conditions)
Biologists have long suspected that the mechanisms of aging would never be understood fully until a better understanding of genetics was obtained. As genetic information has exploded, a number of theories of aging have emerged. Each of these theories has focused on a different aspect of the genetic changes observed in aging cells and organisms. Animal models, from simple organisms such as Tetrahymena (a single-celled, ciliated protozoan) and Caenorhabditis (a nematode worm) to more complex organisms like Drosophila (fruit fly) and mice, have been used extensively in efforts to understand the genetics of aging. The study of mammalian cells in culture and the genetic analysis of human progeroid syndromes (that is, premature aging syndromes) such as Werner’s syndrome and diseases of old age such as Alzheimer’s disease have also improved the understanding of aging. From these data, several theories of aging have been proposed.
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Genetic Changes Observed in Aging Cells (Genetics & Inherited Conditions)
Most of the changes thus far observed represent some kind of degeneration or loss of function. Many comparisons between cells from younger and older individuals have shown that more mutations are consistently present in older cells. In fact, older cells seem to show greater genetic instability in general, leading to chromosome deletions, inversions, and other defects. As these errors accumulate, the cell cycle slows down, decreasing the ability of cells to proliferate rapidly. These genetic problems are partly a result of a gradual accumulation of mutations, but the appearance of new mutations seems to accelerate with age due to an apparent reduced effectiveness of DNA repair mechanisms.
Cells that are artificially cultured have been shown to undergo a predictable number of cell divisions before finally becoming senescent, a state where the cells simply persist and cease dividing. This phenomenon was first established by Leonard Hayflick in the early 1960’s when he found that human fibroblast cells would divide up to about fifty times and no more. This phenomenon is now called the Hayflick limit. The number of divisions possible varies depending on the type of cell, the original age of the cell, and the species of organism from which the original cell was derived. It is particularly relevant that a fibroblast cell from a fetus will easily approach the fifty-division limit, whereas a fibroblast cell...
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Progeroid Syndromes as Models of Aging (Genetics & Inherited Conditions)
Several progeroid syndromes have been studied closely in the hope of finding clues to the underlying genetic mechanisms of aging. Although such studies are useful, they are limited in the sense that they display only some of the characteristics of aging. Also, because they are typically due to a single mutant gene, they represent a gross simplification of the aging process. Several genetic analyses have identified the specific genetic defects for some of the progeroid syndromes, but often this has only led to more questions.
Down syndrome is the most common progeroid syndrome and is usually caused by possession of an extra copy of chromosome 21 (also called trisomy 21). Affected individuals display rapid aging for a number of traits such as atherosclerosis and cataracts, although the severity of the effects varies greatly. The most notable progeroid symptom is the development of Alzheimer’s disease-like changes in the brain such as senile plaques and neurofibrillary tangles. One of the genes sometimes involved in Alzheimer’s disease is located on chromosome 21, possibly accounting for the common symptoms.
Werner syndrome is a very rare autosomal recessive disease. The primary symptoms are severe atherosclerosis and a high incidence of cancer, including some unusual sarcomas and connective tissue cancers. Other degenerative changes include premature graying, muscle atrophy, osteoporosis,...
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Genetic Models of Aging (Genetics & Inherited Conditions)
The increasing understanding of molecular genetics has prompted biologists to propose a number of models of aging. Each of the models is consistent with some aspect of cellular genetics, but none of the models, as yet, is consistent with all evidence. Some biologists have suggested that a combination of several models may be required to adequately explain the process of aging. In many ways, understanding of the genetic causes of aging is in its infancy, and geneticists are still unable to agree on even the probable number of genes involved in aging. Even the extent to which genes control aging at all has been debated. Early studies based on correlations between time of death of parents and offspring or on the age of death of twins suggested that genes accounted for 40 to 70 percent of the heritability of longevity. Later research on twins has suggested that genes may only account for 35 percent or less of the observed variability in longevity, and for twins reared apart the genetic effects appear to be even less.
Genetic theories of aging can be classified as either genome-based or mutation-based. Genome-based theories include the classic idea that longevity is programmed, as well as some evolution-based theories such as antagonistic pleiotropy, first proposed by George C. Williams, and the disposable soma theory. Mutation-based theories are based on the simple concept that genetic systems gradually fall apart from...
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Genome-Based Theories of Aging (Genetics & Inherited Conditions)
The oldest genome-based theory of aging, sometimes called programmed senescence, suggested that life span is genetically determined. In other words, cells (and by extrapolation, the entire organism) live for a genetically predetermined length of time. The passing of time is measured by some kind of cellular clock and when the predetermined time is reached, cells go into a self-destruct sequence that eventually causes the death of the organism. Evidence for this model comes from the discovery that animal cells, when grown in culture, are only able to divide a limited number of times, the so-called Hayflick limit discussed above, and then they senesce and eventually die. Further evidence comes from developmental studies where it has been discovered that some cells die spontaneously in a process called apoptosis. A process similar to apoptosis could be responsible for cell death at old age. The existence of a cellular clock is consistent with the discovery that telomeres shorten as cells age.
In spite of the consistency of the experimental evidence, this model fails on theoretical grounds. Programmed senescence, like any complex biological process, would be required to have evolved by natural selection, but natural selection can only act on traits that are expressed during the reproductive years. Because senescence happens after the reproductive years, it cannot have developed by natural selection. In addition,...
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Mutation-Based Theories of AgingMutationsaging and (Genetics & Inherited Conditions)
The basic premise of all the mutation-based theories of aging is that the buildup of mutations eventually leads to senescence and death, the ultimate cause being cancer or the breakdown of a critical system. The major support for these kinds of theories comes from a number of studies that have found a larger number of genetic mutations in elderly individuals than in younger individuals, the same pattern being observed even when the same individual is assayed at different ages. The differences among the various mutation-based theories have to do with what causes the mutations and what kinds of DNA are primarily affected. As mentioned above, the disposable soma theory also relies, in part, on mutation-based theories.
The most general mutation-based theory is the somatic mutation/DNA damage theory, which relies on background radiation and other mutagens in the environment as the cause of mutations. Over time, the buildup of these mutations begins to cause failure of critical biochemical pathways and eventually causes death. This theory is consistent with experimental evidence from the irradiation of laboratory animals. Irradiation causes DNA damage, which, if not repaired, leads to mutations. The higher the dose of radiation, the more mutations result. It has also been noted that there is some correlation between the efficiency of DNA repair and life span. Further support comes from...
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From Theory to Practice (Genetics & Inherited Conditions)
Many of the genetic theories of aging are intriguing and even seem to be consistent with experimental evidence from many sources, but none of them adequately addresses longevity at the organismal level. Although telomeres shorten with age in individual cells, cells continue to divide into old age, and humans do not seem to die because all, or most, of their cells are no longer able to divide. Cells from older individuals do have more mutations than cells from younger individuals, but the number of mutations observed does not seem adequate to account for the large suite of problems present in old age. Mitochondria, on average, do function more poorly in older individuals and their mtDNA does display a larger number of mutations, but many mitochondria remain high functioning and appear to be adequate to sustain life.
Essentially, geneticists have opened a crack in the door to a better understanding of the causes of aging, and the theories presented here are probably correct in part, but much more research is needed to sharpen the understanding of this process. The hope of geneticists, and of society in general, is to learn how to increase longevity. Presently, it seems all that is possible is to help a larger number of people approach the practical limit of 120 years through lifestyle modification and medical intervention. Going significantly beyond 120 years is probably a genetic problem that will not be solved for...
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Further Reading (Genetics & Inherited Conditions)
Arking, Robert, ed. Biology of Aging: Observations and Principles. 3d ed. New York: Oxford University Press, 2001. An updated edition of a 1990 text that examines such topics as defining and measuring aging, changes in populations, genetic determinants of longevity, and aging as an intracellular process.
Macieira-Coelho, Alvaro. Biology of Aging. New York: Springer, 2002. A solid text that includes many figures, tables, charts, and illustrations.
Manuck, Stephen B., et al., eds. Behavior, Health, and Aging. Mahwah, N.J.: Lawrence Erlbaum, 2000. Examines a host of health care dilemmas associated with the elderly. One section considers the basic tenets of genetic and molecular biology, including some of the methods of looking at heritable differences in health and well-being. Illustrated.
Medina, John J. The Clock of Ages: Why We Age, How We Age—Winding Back the Clock. New York: Cambridge University Press, 1996. Designed for the general reader. Covers aging on a system-by-system basis and includes a large section on the genetics of aging.
Read, Catherine Y., Robert C. Green, and Michael A. Smyer, eds. Aging, Biotechnology, and the Future. Baltimore: Johns Hopkins University Press, 2008. Collection of essays describing how advances in medicine and technology are affecting the aging process and the lives of elderly persons.
Ricklefs, Robert E., and Caleb...
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Web Sites of Interest (Genetics & Inherited Conditions)
Alliance for Aging Research. http://www.agingresearch.org. Provides information on genetics and the aging process, including how the Human Genome Project will affect the future of health and health care.
American Federation of Aging Research. http://www.afar.org. Includes a section called Infoaging.org that provides information on research about the biology and diseases of old age and other aspects of aging.
American Geriatrics Society. http://www.americangeriatrics.org. This national society of health care providers for older persons posts information on genetic screening for such disorders as Alzheimer’s disease.
Gerontological Society of America. http://www.geron.org. The society is devoted to research, education, and practice in the field of aging.
National Institute on Aging. http://www.nia.nih.gov. The institute supports research programs on the biology and genetics of aging and provides the public with information on aging.
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Physical and Psychological Factors (Magill’s Medical Guide, Sixth Edition)
Aging takes place over the course of life, and the rate of change varies between individuals and groups. Differences in aging are genetically determined in part, but there is also a substantial environmental component. These environmental factors can include nutrition, lifestyle choices, and toxins in the environment. Primary aging relates to the genetic components of aging, while secondary aging focuses on environmental factors.
Aging is influenced by a number of normative age-graded factors that typically take place at a particular chronological time. These factors can be biological, as reflected in puberty and menopause, as well as environmental, having an impact on the socialization of the individual, such as the changes needed to enter school or to assume a work role. Normative history-graded factors refer to events that are shared by a society and have an impact, either positive or negative, on the aging process. The Great Depression in the 1930’s, World War II, and the Vietnam War are examples of normative history-graded events. When a major event has an impact on a single generation in a society, it is known as a cohort effect. When an event affects the entire population, it is termed a period effect. The Great Depression is considered to be a period effect, while the Vietnam War is labeled a cohort effect. Normative age-graded factors are considered to be most important during childhood and in...
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Disorders and Effects (Magill’s Medical Guide, Sixth Edition)
Hutchinson-Gilford syndrome and Werner’s syndrome are two forms of accelerated aging called progeria. The person with Hutchinson-Gilford syndrome experiences dwarfism and pseudosenility. Individuals with this genetic form of accelerated aging appear like very old small humans. They usually die in their teenage years of coronary heart disease. Werner’s syndrome, also caused by genetic factors, affects persons in their late twenties and thirties and produces a shortened life span. The afflicted person ages very rapidly and develops a pinched facial expression, cataracts, diabetes, hypogonadism, a beaklike nose, prominent teeth, and a recessive chin.
Dementia is a fairly common condition that increases in frequency with age. It involves deficits in two or more areas of cognition that have a negative impact on daily functioning. Dementia produces impairment of memory and orientation and disruption in the ability to plan, organize, sequence, and make decisions. The majority of persons in old age who experience dementia have Alzheimer’s disease. Current estimates suggest that between 2.5 and 4 million people have this disease. With the expanding size of the elderly population, however, the number of persons with Alzheimer’s disease should increase to 9 million by the year 2025. The risk for Alzheimer’s disease increases by approximately 1 percent with each year of life after age sixty-five. It is a progressive...
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Perspective and Prospects (Magill’s Medical Guide, Sixth Edition)
Historically, the ancient Greeks provided some of the first writings on aging in discussing how old age brings increased anxiety about death. During the Roman era, Cicero suggested ways for elderly people to make themselves useful in advisory and administrative roles. He emphasized the importance of a developed mind and enhanced character as compensations for physical decline. The first manual to describe the problems associated with aging was published in the fifteenth century. Overall, however, historical writers had little to say about the positive attributes of aging.
Many common beliefs about aging have often resulted in oversimplified and biased stereotypes about older adults. These stereotypes may portray elderly persons as uninterested, weak, unattractive, undesirable, rigid, incapable of sexual activity, conservative, and lacking in intellectual acuity. This perspective encourages discrimination against older persons and is termed ageism. Senility is not a medical term but is commonly used in U.S. society. It implies that old people lose the intellectual capacity to make intelligent decisions. As the number of older adults has increased and the importance of scientific investigations of aging has been expanded, positive counterpoints to aging have emerged. A new realistic image of older adults portrays the healthy elderly population as resourceful, optimistic, intelligent, flexible, and sexual beings. The...
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For Further Information: (Magill’s Medical Guide, Sixth Edition)
Arking, Robert. The Biology of Aging: Observations and Principles. 3d ed. Boston: Oxford University Press, 2006. This is a comprehensive review of the age-related changes in all biological systems. The author provides the most up to date research findings and clinical observations related to aging processes.
Cohen, Gene D. The Mature Mind: The Positive Power of the Aging Brain. New York: Basic Books, 2006. The author provides a counterargument to the contention that the aging brain experiences only declines in function. He suggests that there are positive changes that are often ignored or not identified by researchers.
Eaton, William W., ed. Medical and Psychiatric Comorbidity over the Course of Life. Washington, D.C.: American Psychiatric Publishing, 2006. The author provides a comprehensive review of the psychiatric and medical conditions common to old age. The book is written for the health care professional to understand how the processes of aging impact on physical and mental health.
Hill, Robert D. Positive Aging: A Guide for Mental Health Professionals and Consumers. New York: W. W. Norton, 2006. Argues that even with the diminished physical and mental capacities associated with aging, the older adult can experience positive aging. The author provides specific strategies to overcome the age-related declines of late life.
Markut, Lynda A., and...
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Aging (Encyclopedia of Medicine)
Starting at what is commonly called middle age, operations of the human body begin to be more vulnerable to daily wear and tear; there is a general decline in physical, and possibly mental, functioning. In the Western countries, the length of life is often into the 70s. The upward limit of the life span, however, can be as high as 120 years. During the latter half of life, an individual is more prone to have problems with the various functions of the body and to develop any number of chronic or fatal diseases. The cardiovascular, digestive, excretory, nervous, reproductive and urinary systems are particularly affected. The most common diseases of aging include Alzheimer's, arthritis, cancer, diabetes, depression, and heart disease.
Human beings reach a peak of growth and development around the time of their mid 20s. Aging is the normal transition time after that flurry of activity. Although there are quite a few age-related changes that tax the body, disability is not necessarily a part of aging. Health and lifestyle factors together with the genetic makeup of the individual, and determines the response to these changes. Body functions that are most often affected by age include:
- Hearing, which declines especially in relation to the highest pitched tones.
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Aging (Encyclopedia of Psychology)
The process by which the human body changes and matures over time, especially the means by which dying cells are not replaced in sufficient numbers to maintain current levels of function; the process by which human behavior alters with time.
Psychological studies of aging populations began in earnest in the late nineteenth century when psychologists found that mental abilities deteriorated with age. These abilities included memory and the types of mental performance measured in IQ tests. In some individuals, verbal abilities were shown to deteriorate with advanced age, although at a slower rate than other skills; with others, verbal abilities, especially vocabulary, may increase with age. Such data have often been corroborated in tests with chimpanzees, where younger animals perform better in tests of memory and other such areas of mental functioning. For decades, then, it was assumed that the physical deterioration of the body, so evident in the elderly, was surely matched by a similar decline in the mind.
Recent studies, however, have begun to cast doubt on these assumptions. One area where current research has disproved a long-held belief about the aging of the mind is in the death of neurons, formally thought to necessarily lead to diminished mental functioning. It is now known that the brain has far more neurons...
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Aging (Encyclopedia of Alternative Medicine)
Starting at what is commonly called middle age, operations of the human body become more vulnerable to daily wear and tear. There is a general decline in physical, and possibly mental, functioning. In the Western countries, the length of life often extends into the 70s. However, the upward limit of the life span can be as high as 120 years. During the latter half of life, an individual is more prone to problems with the various functions of the body, and to a number of chronic or fatal diseases. The cardiovascular, digestive, excretory, nervous, reproductive, and urinary systems are particularly affected. The most common diseases of aging include Alzheimer's, arthritis, cancer, diabetes, depression, and heart disease.
Human beings reach a peak of growth and development during their mid 20s. Aging is the normal transition time after that flurry of activity. Although there are quite a few age-related changes that tax the body, disability is not necessarily a part of aging. Health and lifestyle factors, together with the genetic makeup of the individual, determine the response to these changes. Body functions that are most often affected by age include:
- Hearing, which declines especially in relation to the highest pitched tones.
- The proportion of fat...
(The entire section is 2150 words.)