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Sir Vithaldas Thackersey College of Home Science

Ms. Zainab Patharia

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aging theories biology of aging human aging gerontology

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These notes provide an overview of various theories related to the aging process, categorized into biological, sociologic, psychologic and moral/spiritual dimensions. They examine the role of genetics, hormones (like growth hormone and sex hormones), and the immune system in the aging process. Damage/error theories, like the free radical theory and glucose crosslinking theory are also reviewed.

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1 THEORIES OF AGING Aging may be seen as a sequence of events that occur from conception to death. Categories of aging theories all seek to explain and explore t...

1 THEORIES OF AGING Aging may be seen as a sequence of events that occur from conception to death. Categories of aging theories all seek to explain and explore the many dimensions of aging. 1. Biologic: Interested with answering fundamental questions with respect to the physiologic processes that occur in all living organisms over time. 2. Sociologic: Looking at the roles and relationships within which individuals engage in later life. 3. Psychologic: Controlled by biology and sociology; address how a person responds to the engagements of their age. 4. Moral/Spiritual: Study how an individual seeks to validate his or her existence. Many theories have been proposed to explain the process of aging, but neither of them appears to be fully satisfactory. The traditional aging theories hold that aging is not an adaptation or genetically programmed. Modern biological theories of aging in humans fall into two main categories: programmed and damage or error theories. The programmed theories imply that aging follows a biological timetable, perhaps a continuation of the one that regulates childhood growth and development. This regulation would depend on changes in gene expression that affect the systems responsible for maintenance, repair and defense responses. The damage or error theories emphasize environmental assaults to living organisms that induce cumulative damage at various levels as the cause of aging. The programmed theory has three sub-categories: 1) Programmed Longevity - Aging is the result of a sequential switching on and off of certain genes, with senescence being defined as the time when age-associated deficits are manifested. Programmed Cell Death – in humans each cell can divide only a limited number of times i.e. about 50. Once this number is reached the cell succumbs. If the cell division can be increased the life span can also increase. Tortoise cells divide 140 times, so the life span is 200 years. 2) Endocrine Theory - Biological clocks act through hormones to control the pace of aging. Recent studies confirm that aging is hormonally regulated and that the evolutionarily conserved insulin/IGF-1 signaling (IIS) pathway plays a key role in the hormonal regulation of aging. Hormones: a. Growth hormone, the product of pituitary gland appears to play a role in body composition and muscle and bone strength. There is a decrease in the production of growth hormone during aging. b. Sex hormones – levels of estrogen and testosterone tend to fall off. Estrogen produced by ovaries slows the bone thinning that accompanies aging and may help prevent frailty and disability. Low levels of testosterone produced in testes decreases muscle strength. c. Melatonin secreted by the pineal gland declines during aging which triggers changes throughout the endocrine system. d. Dehydroepiandrosterone (DHEA): is produced in the adrenal glands. It is a weak male Compiled by: Ms. Zainab Patharia Faculty at Sir Vithaldas Thackersey College of Home Science 2 hormone and a precursor to some other hormones. Decreased levels of this hormone is related to decline in immune systems, and increased prevalence of chronic diseases, like cancer and multiple sclerosis. Hormone replacement – 1. Estrogen replacement therapy in women lessens the accelerated bone loss that comes with menopause and may help prevent cardiovascular disease. Testosterone therapy has benefits for aging men, by increasing bone and muscle mass and strength, but both the sex hormone therapies may lead to cancer and other risks. DHEA sulfate - boosts the levels of interleukin-2, important in the immune response. 3) Immunological Theory - The immune system is programmed to decline over time, which leads to an increased vulnerability to infectious disease and thus aging and death. It is well documented that the effectiveness of the immune system peaks at puberty and gradually declines thereafter with advance in age. For example, as one grows older, antibodies lose their effectiveness, and fewer new diseases can be combated effectively by the body, which causes cellular stress and eventual death. Indeed, dysregulated immune response has been linked to cardiovascular disease, inflammation, Alzheimer’s disease (AD), and cancer. Although direct causal relationships have not been established for all these detrimental outcomes, the immune system has been at least indirectly implicated Damage or error theories 1. Free radical theory of aging: damage caused by oxygen radicals is responsible for many of the bodily changes that come with aging. Free radicals have been implicated not only in aging but also in degenerative disorders, including cancer, atherosclerosis, cataracts, and neurodegeneration. Oxygen radicals are formed as a byproduct of normal metabolism, when food and oxygen are turned into energy by cells. The highly reactive oxygen radical with its unpaired electron combines with other molecules, damaging proteins, cell membranes and DNA; the DNA molecules found in mitochondria are especially susceptible. Defense mechanism: but free radicals do not go unchecked. Mounted against them is a multilayer defense system manned by antioxidants that react with and disarm these damaging molecules. Antioxidants include nutrients – the familiar Vitamin C & E, β Carotene as well as enzymes such as superoxide dismutase (SOD), catalase, and glutathione peroxidase. Free radical hypothesis – SOD helps convert the oxygen radical superoxide into hydrogen peroxide (also harmful), which is then converted with the help of catalase into oxygen and water. Increase levels of SOD, catalases & antioxidants decreases oxidative damages and promotes longer life span. Vit C decreases risk of Heart-disease by blocking oxidation of LDL. Oxidation of these cholesterol carrying proteins is thought to be a key element in hardening of the arteries. Vit.E also decreases the risk of heart attacks. 2. Glucose Crosslinking Theory: Another suspect in cellular deterioration is blood sugar or glucose. In a process called non-enzymatic glycosylation or glycation, glucose molecules attach themselves to proteins, setting in motion a chain of chemical reactions that ends in the proteins binding together or crosslinking, thus altering their biological and structural roles. Crosslinks, which have been termed advanced glycosylation end products (AGEs), seem to toughen tissues and may cause some of the Compiled by: Ms. Zainab Patharia Faculty at Sir Vithaldas Thackersey College of Home Science 3 deterioration associated with aging. AGEs have been linked to stiffening connective tissue (collagen), hardened arteries, clouded eyes, loss of nerve function, and less efficient kidneys. This condition may also appear at younger ages in people with diabetes. Diabetes is sometimes considered an accelerated model of aging. Defense mechanism: Immune system cells called macrophages combat glycation. Macrophages with special receptors for AGEs seek them out, engulf them, break them down & eject them into the bloodstream where they are filtered out by the kidneys and eliminated in urine. The only drawback is the immune system decreases with advancing age. To combat this, anti-aging drugs against AGEs are being used. 3. DNA Repair: In the normal wear and tear of cellular life, DNA undergoes continual damage. Attacked by oxygen radicals, ultraviolet light, and other toxic agents, it suffers damage in the form of deletions, or destroyed sections, and mutation, or changes in the sequence of DNA bases that makeup the genetic code. DNA damage gradually leads to malfunctioning genes, proteins, cells and deteriorates tissues and organs. DNA is damaged throughout life, the repair process may be a major factor in aging, health, and longevity. Repair rates can vary among cells, with the most efficient repair going on in germ (sperm and egg) cells. Moreover, certain genes are repaired more quickly than others, including those that regulate cell proliferation. Mitochondrial DNA damage increases with age, and several diseases that appear late in life, including late-onset diabetes. 4. Heat Shock Proteins: Produced in response to any stress. HSPs decline with age. HSPs are known to help the cell disassemble and dispose of damaged proteins and to facilitate the making and transport of new proteins. HSP-70 appears to closely resemble hormones released in response to stress such as glucocorticoids and catecholamines. 5. Growth/ Trophic Factors (chemical messengers) – mediate GH, stimulate cell activities, size, functioning of skeletal muscles. GH stimulates production of insulin-like growth factor IGF -1 in the liver and then enters and flows through the bloodstream, seeking out special IGF-1 receptors on the surface of various cells, including muscle cells. Through these receptors it signals the muscle cells to increase in size & number, perhaps by stimulating their genes to produce more special muscle specific proteins. The action of exercise stimulates a certain amount of GH secretion on its own, and Obesity which depresses production of GH. Lower levels of GH have been linked to excess abdominal fat but not to lower body fat. Build-up of toxic materials e.g. lipofuscin or breakdown products of lipids hamper metabolic processes. 6. Error theory - based on the idea that errors can occur in the transcription of the synthesis of DNA. These errors are perpetuated and eventually lead to systems that do not function at the optimum level. The organism’s aging and death are attributable to these events. 7. The Membrane Theory of Aging - According to this theory it is the age-related changes of the cell's ability to transfer chemicals, heat and electrical processes that impair it. As we grow older the cell membrane becomes less lipid (less watery and more solid). This impedes its efficiency to conduct normal function and in particular there is a toxic accumulation Compiled by: Ms. Zainab Patharia Faculty at Sir Vithaldas Thackersey College of Home Science 4 8. The Decline Theory -The mitochondria are the power producing organelles found in every cell of every organ. Their primary job is to create Adenosine Triphosphate (ATP) and they do so in the various energy cycles that involve nutrients such as Acetyl-L-Carnitine, CoQ10 (Idebenone), NADH and some B vitamins etc.] Enhancement and protection of the mitochondria is an essential part of preventing and slowing aging. Enhancement can be achieved with the above nutrients, as well as ATP supplements themselves. Emerging theories They include the following: 1. Neuroendocrine Control or Pacemaker Theory: The neuroendocrine system controls many crucial activities concerning growth and development. Researchers are looking into the roles that the hypothalamus and the hormones DHEA (dehydroepiandrosterone) and melatonin play in the aging process. DHEA, secreted by the adrenal glands, reduces over the lifetime of an individual. Giving this hormone to laboratory mice increases longevity, bolsters immunity, and makes the animals appear younger. These mice also ate less, so possibly DHEA-fed mice display the effect of calorie restriction. Melatonin, a hormone, is produced by the pineal gland, is a regulator of biologic rhythms and a powerful antioxidant that may enhance immune function. The level of melatonin production in the body declines dramatically from just after puberty until old age. 2. Metabolic Theory of Aging/Caloric Restriction: This theory proposes that all organisms have a limited metabolic lifetime and that organisms with a higher metabolic rate have a shorter life span. Research showing that certain fish, when the water temperature is lowered, live longer than their warm water counterparts is used to validate this. Extensive experimentation on the effects of caloric restriction on rodents has demonstrated that caloric restriction increases the lifespan and delays the onset of age-dependent diseases. Compiled by: Ms. Zainab Patharia Faculty at Sir Vithaldas Thackersey College of Home Science 5 3. DNA-Related Research: Two developments are occurring at this time in relationship to DNA and the aging process: One, as scientists continue to map the human genome, they are identifying certain genes that play a role in the aging process: Two, the discovery of telomeres, located at the ends of chromosomes, which may function as the cells’ biologic clocks. Spiritual Theories Examine how an individual seeks to explain and validate his or her existence. The research on religiosity or spirituality and health is controversial. Some consider it to be unscientific to study religiosity among other health determinants. Despite this it seems an intensification of spiritual affectations occurs with aging, and the scientific community needs to explore the connection between religiosity, spirituality and health in order to more fully understand spiritualities' effect on aging. Psychological Theories Influenced by both biology and sociology; address how a person responds to the tasks of his or her age. The earliest known theories on aging were known to be psychological theories. They include: Compiled by: Ms. Zainab Patharia Faculty at Sir Vithaldas Thackersey College of Home Science 6 ➔ Human Needs Theory: focuses on the fact that human behavior is motivated by their needs with age. Namely; physiological, safety and security, love and belongingness, self-esteem, and actualization. ➔ Life-Course (Lifespan development) Theory: Came into existence in the 1980s by behavioral psychologists who decided to shift from personality development as the basis of understanding aging to the concept of ‘life course’. This theory divides life course into a predictable pattern of stages that are formed according to goals, relationships and internal values. This theory focuses on the interconnectedness of individuals and society. ➔ Disengagement Theory: Refers to an inevitable process in which many of the relationships between a person and other members of society are severed & those remaining are altered in quality. Withdrawal may be initiated by the aging person or by society, and may be partial or total. It was observed that older people are less involved with life than they were as younger adults. As people age, they experience greater distance from society & they develop new types of relationships with society. In America there is evidence that society forces withdrawal on older people whether or not they want it. Some suggest that this theory does not consider the large number of older people who do not withdraw from society. This theory is recognized as the first formal theory that attempted to explain the process of growing older. ➔ Activity Theory: describes the psychosocial aging process. emphasizes the importance of ongoing social activity. Suggests that a person's self-concept is related to the roles held by that person i.e. retiring may not be so harmful if the person actively maintains other roles, such as familial roles, recreational roles, volunteer & community roles. To maintain a positive sense of self the person must substitute new roles for those that are lost because of age. And studies show that the type of activity does matter, just as it does with younger people. Compiled by: Ms. Zainab Patharia Faculty at Sir Vithaldas Thackersey College of Home Science

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