What are theories on aging?

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Aging is an entropic (energy-disorder) phenomenon that is exhibited by most multicellular organisms. Two major theories—the free radical theory and the genetic programming theory—have been suggested to explain the mechanisms of aging. Although each theory emphasizes different aspects of the aging process, they almost certainly are interrelated.
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The aging process occurs in all living organisms, although it is most pronounced in vertebrate animals, animals having a cartilaginous, bony endoskeleton, an efficient heart, and a highly developed nervous system. It is part of the basic sequence of animal development from conception to reproductive maturity to death. It follows the second law of thermodynamics, a physical principle of the entire universe that maintains that the disorder (entropy) of the universe is constantly increasing because of the dissipation of energy and the gradual transfer of energy from system to system. Living organisms age because of the inefficiency of the chemical reactions within their cells, thereby creating disorder as is evidenced by breakdowns in physiological rhythms (for example, nerve cell functioning, blood pressure changes, and reduced kidney filtration) and physical structure (for example, bone deformations, muscle weakness, and hair loss). The second law of thermodynamics maintains that no machine is 100 percent efficient; therefore, energy will be lost continuously with accompanying decay of the system, or body.

Physiological Aging

In humans and other mammalian species, the process of aging follows a very predictable pattern. An individual is conceived by the union of genetic information from the mother via an egg and the father via sperm, thereby producing a single-celled zygote. By the connected processes of mitosis (chromosome duplication followed by separation) and cytokinesis (cell division), the zygote divides into two cells, which later divide to make four cells, then eight cells, and so on until an individual composed of approximately 100 trillion cells is produced. Very early in development (for example, a few hundred cells), different cells in various locations begin to specialize, or differentiate, by hormonally initiated changes in gene expression within these cells, thereby giving rise to specialized structures such as nerves, muscle, skin, bone, eyes, and fingers.

After the individual organism is fully developed and can survive in the environment on its own, it will either exit the mother’s body or hatch from a protective egg case, or shell. Subsequent juvenile development will include brain neuronal changes (plasticity) as a result of learning and social interactions, and physiological changes, leading to sexual maturity, or adulthood. Development up to adulthood does technically constitute aging, although there is little evidence of physiological decay. Various hormones, particularly steroid hormones, are prominent during a person’s sexual stage, when the individual is capable of sexual reproduction. Individuals are at their physical peak during the reproductive period. At the end of the critical reproductive period (menopause in women), the degenerative physical effects of true aging become very evident and accelerate with time as the individual becomes older. In a biological sense, the purpose of an organism is to reproduce and continue the transfer of genetic information. By age fifty or so, both men and women should have achieved this objective, and estrogen (in women) and testosterone (in men) begin a more rapid decline. Consequently, the individual organism begins a progressive deterioration after age fifty or so toward death, thereby making room in the environment for its descendants. This is a harsh, but real, view of an organism’s life. The key to understanding why deteriorative aging occurs lies in the hormones, chemicals, and cellular changes that are present in the organism just before this stage.

Among the physical changes of aging that are evident very early are heart and respiratory changes. On birth, the average human newborn has a pulse of 120 heartbeats per minute, a breathing rate of forty to forty-five breaths per minute, and a blood pressure of 60/30. These data indicate a very high metabolic rate in individuals during early development. As humans age, both pulse and breathing rates decrease, whereas blood pressure increases. The average healthy adult has a pulse of approximately 60 to 80 heartbeats per minute, a breathing rate of approximately eight to twelve breaths per minute, and a blood pressure somewhere around 120/70. Neuronal plasticity of the brain and, therefore, learning peak during the early reproductive years and decline around the age of forty-five to fifty. Most physiological processes undergo a steady decline from age twenty or so, with steeper declines occurring near age fifty, although large individual variation exists.

Theories of Aging

When an organism dies, the electrical activity of billions of brain neurons ceases, along with cessation of heart and respiratory muscle contractions. In more than 80 percent of human deaths by “natural causes,” however, the exact cause of death cannot be determined. The physiological causes of aging and death remain poorly understood, although more than three hundred theories have been proposed to explain the process. Of all the theories proposed, two—the free radical theory and the genetic programming theory—have withstood vigorous testing and continue to be widely studied. Although each theory emphasizes different aspects of cellular aging, they are complementary and both may be correct in their combined interpretations.

Free Radical Theory

The role of free radicals in cell damage and aging was first proposed by Denham Harman in 1972. The free radical theory of aging maintains that the degenerative events that occur within the cell and the entire organism during aging are caused by the toxic effects of oxidizing free radical molecules. Free radicals are molecules that have a free extra electron per molecule that can be donated to another molecule. As a result, free radicals are highly reactive with most substances that they encounter. Their chemical reaction with a recipient molecule may affect the structure and function of that molecule so that it does not function properly. In a living cell, such an event could have disastrous consequences. The deoxyribonucleic acid (DNA) nucleotide sequence of any gene could be mutated, or altered, by a free radical, thereby altering the structure or function of the protein encoded by that gene and affecting all cellular functions controlled by that specific protein. If the protein is essential for the cell’s survival, the result could be cellular death or cellular transformation to the cancerous state.

Free radicals such as superoxide, hydroxyl radical, and hydrogen peroxide are naturally produced as by-products of the cell’s metabolic activities. The cells of most living organisms produce antioxidant enzymes such as catalase, glutathione peroxidase, and superoxide dismutase to scavenge and inactivate free radicals wherever they occur. No such capture operation is 100 percent efficient, however. Some free radicals react with cellular molecules; the accumulated effects of these reactions over time may be responsible for cellular aging. Antioxidants, such as vitamins C and E, block free radicals and are suggested for prolonging life. These antioxidant chemicals are frequently cited as the basis of claims for the benefits of consuming a diet rich in fruit and vegetables. However, antioxidant supplementation has not yet been proven to extend life. Although phenybutylnitrone was shown to produce about a 10 percent extension of the life span in animals, the results of this experiment have not been reproduced. Of all the theories of aging, Harman’s free-radical theory has the most consistent experimental support. However some models demonstrate that increased oxidative stress has no effect on life span. Thus, more data are needed to decisively determine the role of free radicals in aging.

Genetic Programming Theory

The genetic programming theory of aging maintains that the cells of all living organisms contain genes that encode signaling protein hormones. These hormones, when produced, elicit aging-related changes within the cells at specific times during the organism’s development, including death. Another viewpoint within this theory is that the cells of various tissues within living organisms are programmed to die after undergoing a specified number of genetically encoded divisions. Some studies in gene theory suggest it is the altering of genes over time that causes aging. In addition, because observations of older people demonstrate an increase of mutated genes, it is also theorized that gene mutations over time cause aging. Indeed, cancer is often the result of mutations. Molecular biology underlies the more recent theories on aging. Cells keep dividing until they can no longer divide and then they simply die. Embryonic cells divide much more than cells from adults. Hence, this theory proposes that cell division holds the key to the mechanics of human aging. Other nonbiological theories of aging include disengagement, activity, selectivity, and continuity theories. Additional biological theories include telomere, reproductive-cell cycle, wear-and-tear, evolutionary, accumulative-waste, autoimmune, aging-clock, and cross-linkage theories.

Applying Theories to Health and Disease

By the start of the twenty-first century, researchers in laboratories throughout the world had begun actively investigating the mechanisms of the aging process. The problem was being tackled from many different perspectives, including biochemical, genetic, physiological, gerontological, psychological, and sociological approaches. The topic is of particular interest in countries such as the United States, where the overall population is becoming progressively older. Although much of the research has been devoted to medical care for the elderly, many scientists have begun exploring the biochemistry of aging with hopes of understanding the process and possibly slowing or reversing it.

The two principal theories of aging (senescence), when combined, provide a very good working model for attacking the aging problem. The free radical theory of aging provides the cause, and the genetic programming theory provides an overall developmental view of the phenomenon. There can be no question that there are certain genes within all living cells that in a step-by-step manner control the sequential development of the entire organism. At the same time, free radical molecules are constantly being produced within body cells, and these same cells are being exposed to mutagenic (mutation-causing) radiation and chemicals. These substances will cause accumulated cellular damage over time, even with the body’s combined defenses of antioxidant enzymes, immune system cells, and kidney filtration of impurities from blood. These defenses work extremely well up to the end of the individual’s reproductive period; then, they decline rapidly, almost as if they were programmed to do so.

Recent studies have shown that calorie restriction, which limits the intake of energy, reduces free radicals and increases the life span of rodents. Severely reducing calories by restricting the number of meals and fasting has been shown to suppress the development of various diseases and to increase the longevity of life in rodents by 30 to 40 percent. However, severely reducing calories by 50 percent or more resulted in death. In addition, for caloric restriction, which lengthens the time between cell divisions, to be beneficial, it must be started early in life because age, at the molecular level, is counted as the number of cell doublings. Drug companies have begun searching for methods to mimic the beneficial effects of caloric restriction without severely limiting food intake.

Among humans, several unusual pathologies are of interest to scientists who research aging. Among these is the disease called progeria, a condition in which the aging process is greatly accelerated. The aging process is also emphasized in acquired immunodeficiency syndrome (AIDS) and the genetic disorder called autoimmune deficiency syndrome. In both situations, an individual’s entire immune system is rendered useless, thereby leaving the individual’s body defenseless against the continuous onslaught of usually harmless bacteria, viruses, and mutations.

Cancer is one of the leading causes of death, and the incidence of cancer increases as people age. Cancer is essentially a disease of uncontrolled cell growth, which interferes with the normal functions of the body. There are several dozen types of cancer, based on the affected tissues, site of the cancer in the tissue, and cell type that is affected. Causes of cancers are believed to be both genetically and environmentally defined; that is, some people are genetically more susceptible to environmental insults than others. Scientists believe that all cancers begin with one cell that becomes damaged and is not stopped from dividing and creating new damaged cells. An important scientific discovery has been the identification of certain genes involved in the development of cancerous cells: the proto-oncogenes and the tumor-suppressor genes. How cancer relates to death is complex and continues to be debated. Until more research is completed, it will not be known with certainty whether aging-related changes in cells and their systems make them more susceptible to cancer, or whether advancing time just allows more genetic hits to accumulate and produce cancerous cells.

The process of aging is difficult to measure, describe, or quantify, although it is a process that every organism experiences. Aging is a focus of many sciences, including physiology, chemistry, biochemistry, and genetics. As a scientific process, aging must have a beginning and an end, a substrate and a product, and a reason for the metabolic change; however, the scientific process of aging is not yet understood.

Psychological Perspective

The process of aging occurs within all living organisms. Theories describing the mechanisms of aging are of relevance to psychology because the aging process is a developmental process that encompasses all bodily systems, including the brain and central nervous system. Aging is a fundamental focal point of consciousness, religious beliefs, and social structure. Simply, people are afraid of dying. As a result, aging is incorporated into human religions, behavior, and culture. Society stresses youthfulness, so humans go to great lengths and expense to reverse the effects of aging with skin creams, baldness cures or coverups, clothing, bodybuilding, cosmetic injections, and plastic surgery. Psychologists have found that negative stereotypes about aging can actually shorten life and that people who have a positive perception of aging live seven and a half years longer than those who have a negative view.

Psychology is a phenomenon of intelligent living organisms, and living organisms are complex entities consisting of intricate chemical reactions. These biochemical reactions, which are responsible for all aspects of life, follow the fundamental physical and chemical properties of the universe. One of these physical processes is the second law of thermodynamics, which maintains that any system loses energy because of inefficiency and therefore becomes more disordered, or entropic. Therefore, aging is an entropic process for the entire universe. Living organisms do undergo a building process during early development that is antientropic; however, after a certain time, specifically the end of the reproductive period, entropy takes over and accelerates. All aspects of the living animal, including the brain, deteriorate.

The free radical and the genetic programming theories of aging have provided scientists with greater insights into the mechanisms of the aging process. These theories also give researchers ideas for attacking aging as a disease that can be treated. Although the so-called fountain of youth represents wishful thinking, research on aging realistically can lead to the prolongation of human life and improvement of the quality of human life. Aging research may help eliminate or treat maladies such as heart disease, Alzheimer’s disease, cancer, and general aging-related declines in most bodily functions.

One factor that permeates human biology in terms of aging, disease, and abnormal psychological behavior is stress. Research has repeatedly linked stress with accelerated aging, increased susceptibility to many diseases (including cancer), decreased mental agility and memory, and insanity. Indeed, scientific research demonstrates that stress speeds the aging process by harming DNA. The rise in the human population and continuing technological growth have been paralleled by a rapid increase in individual stress levels; stress-related diseases such as heart disease, stroke, and cancer; acts of violence, devastating wars, torture, exploitation, and destruction of human life; and the use of alcohol and illegal drugs in an attempt to relieve stress. Reevaluation of the way that one treats fellow humans, a slowing of the fast-paced society, major social reforms, and medical advances in the treatment of stress all will be needed for decreasing stress, a major killer and contributor to the aging process.

Advances in biochemical and genetic medical research probably will produce the means for extending life within the twenty-first century. Regardless of whether human longevity is extended, aging will continue. As it does, researchers will continue to study how and why people age and the consequences of aging for both the individual and the community.


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