Aging in Today's Environment (1987) / Chapter Skim
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6 Environmental Effects on Age-Associated Diseases and Changes in Organ Function
6 Environmental Effects on Age-Associated Diseases and Changes in Organ Function
Pages 109-144
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From page 109... ...
For other diseases, such as those reflecting cumulative, chronic exposures, rates might increase with age. Susceptibility to disease changes throughout the human life cycle and is believed to be a function of many factors, including changes in the immune system and in the rate of cellular division.
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From page 110... ...
) competence Exacerbation of autoimmune reactions Emphysema, cancer Atherosclerotic heart disease Reduced dietary protein Reduced caloric intake Procainamide, estrogen Cotton dust, tobacco smoking Dietary lipids diseases in specific organ systems.
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From page 111... ...
The premenopausa] and postmenopausal incidence curves for breast cancer in different countries suggest that environmental factors play more important roles in the etiology of postmenopausal breast cancer, whereas genetic, endocrinologic, and other endogenous factors strongly influence premenopausal disease (Figure 6-1~.
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From page 112... ...
Mortality from heart disease accounted for approximately half the overall decline during the period, and that from cerebrovascular disease accounted for another 25% of the overall decline. Heart and cerebrovascular diseases account for the largest and third largest mortality rates, respectively, in this age group.
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From page 113... ...
In fact, cancer mortality rates (all sites combined) increase rapidly in middle age and then more slowly with age to 65.
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From page 114... ...
Before epidemiologic observations associating cancer mortality with aging processes can be fully evaluated, several considerations are essential. Smoking is the most likely cause of the increase in respiratory cancer mortality, and cancer mortality in general, among elderly men and women.
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From page 115... ...
. 1940 1950 1960 1970 1980 YEAR FIGURE 6-4 Age-adjusted cancer death rates for selected sites, males: United States, 1930-1978.
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From page 116... ...
It is estimated that cigarette smoking alone accounts for 8~85~o of lung cancer mortality and 30~o of all cancer mortality (Doll and Peto, 1981~.
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From page 117... ...
. It has been suggested that the reason for the rising incidence of cancer with increasing age might be aging of the immune system itself, but the available epidemiologic evidence does not support this view except for some tumors.
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From page 118... ...
1 , 1 20 - 30~ 24 AGING IN TODAY'S ENVIRONA~NT 8 000 7~000 pi m :~ 8 lo lo o 2,000 ~ 1,000 o at 6,000 `, 5,000 r In 4,000 ~ in 3,000 o 70- 8074 84 i incidence and mortality rates Brady (1983) and Brady and of such factors as time-related cumulative damage and the physiologic changes associated with aging that can affect susceptibility makes it apparent that there might not be a single answer to the question of the relation between increasing age and cancer susceptibility, and that the relation varies with target organ, cell type, toxic exposure, and animal species (Birnbaum, 1987~.
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From page 119... ...
Mortality rates by age group for diseases of the heart, influenza and pneumonia, cerebrovascular disease, arteriosclerosis, and accidents show a marked increase in risk with increasing age, whereas rates for other causes such as cancer, diabetes mellitus, bronchitis, emphysema and asthma, and nephritis and nephrosisindicate a more modest increase (Table 6-2~. Mortality due to cirrhosis of the liver does not appear to be associated with increasing age in the elderly population.
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From page 120... ...
Research on human aging processes and the impact of environmental factors has been increasingly constrained by declining autopsy rates. Many reasons have been given for the decline ir1 autopsy rates (American Medical Association, Council on Scientific Affairs, 1987)
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From page 121... ...
In addition, the existence of a system to ensure the collection, study, and storage of relevant tissues, cells, and body fluids would support studies of body burdens of environmental agents and the consideration of potential causal associations of these agents with tissue changes. SKIN Environmental factors are widely suspected of contributing to the effects of the aging processes and to age-associated pathologic conditions, but there are few examples.
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From page 122... ...
Cigarette smoking is a second environmental factor that has been repeatedly noted to produce premature aging of the skin, most recently in a prospective blinded study controlled for age, social class, exposure to the sun, and recent weight change (Model, 1985~. Among 116 patients aged 3~69, those who had smoked at least 10 cigarettes per day for at least 10 years were far more likely than nonsmokers to have deeply wrinkled, atrophic, leathery skin.
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From page 123... ...
, that culture life span is inversely related to donor age (Martin et al., 1970; Schneider and Mitsui, 1976) , and that culture life span is decreased relative to that of cultures from ag~matched control donors for fibroblasts derived from people with some disorders considered to represent premature aging (Martin et al., 1970~.
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From page 124... ...
However, it will not be easily accompILshed. In middle-aged or elderly people, even casual comparison of habitually exposed versus protected sites (e.g., face or hand versus buttock or breath immediately suggests different aging rates, with lines of demarcation corresponding to clothing styles, rather than to anatomic compartments.
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From page 125... ...
Population studies have shown a striking difference between the United States and India in the age-specific prevalence of cataracts: for the age groups 52-64, 6~74, and 7~85, rates were Who, 18%, and Who, respectively, in the United States and 29~o, Who, and 82~o in India. Major identified risk factors related to the etiology of ages related cataract include the following: · Sex.
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From page 126... ...
The increased sorbito} concentration pros duces an osmotic gradient, draws water from the aqueous humor into the lens fibers, causes the lens fibers to swell and eventually become disrupted, and finally produces opacification of the lens. The enzyme aldose reductase produces the sorbitol, and agents that inhibit it have prevented experimental cataracts (Kador et al., 1985~.
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From page 127... ...
A recent examination of pathogenetic factors of aging-related macular degeneration indicates that risk factors include drusen, choroidal vascular disease, and vitamin C deficiency (FeeneyBurns and Ellerseick, 1985~. Drusen, small yellowish bodies
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From page 128... ...
, and an age-related decline in neural function might alIc~w previously silent neurotoxic disorders to reach clinical expression (Caine et al., 1986~. Clinical experience with therapeutic drugs has indicated that the elderly, especially those with metabolic abnormalities or with hepatic or renal impairment, are more susceptible to the toxic effects of xenobiotic
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From page 129... ...
Sleeping patterns are altered. Neurobehavioral changes that accompany human aging are associated with structural or functional alterations in the central and peripheral nervous systems.
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From page 130... ...
The volume of lipofuscin, a yellow, insoluble pigment, increases linearly in most neurons with increasing age, but there is no evidence that this material is cytotoxic. Other neuronal abnormalities in aged brains include neurofiW rilIary tangles, neuritic plaques, and granulovacuolar bodies.
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From page 131... ...
Presenile dementia of the Alzheimer type, Park~nson's disease, and amyotrophic lateral sclerosis are proposed to derive from environmental subclinical damage to specific regions of the central nervous system that are particularly vulnerable to age-related neuronal attrition. For parkinsonism, the hypothesis is being tested in people with subclinical damage to the substantia nigra after exposure to MPTP (Langston, 1985~.
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From page 132... ...
The worldwide problem of substance abuse particularly of ethanol, hallucinogens, narcotics, central nervous system stimulants, solvents, and nitrous oxide- leads to various types of short- or iong-lasting necrologic dysfunction. Many other substances encountered in the workplace (e.g., solvents, monomers, and catalysts)
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From page 133... ...
Drugs that have been reported to cause dementia can be grouped into four main categories: psychotropic medications, such as phenothiazines, butyrophenones, benzodiazepines, tricyclic antidepressants, and lithium carbonate; anticonvulsants, such as phenytoin, mephenytoin, and carbamazepine; antihypertensive agents, such as clonidine, methyIdopa, and propranolol; and anticholinergic compounds, such ~ atropine and antihistamines. Heavy metals including react, mercury, thallium, and arsenic~an cause intellectual impairments that are reversible by chelation or reduction of exposure.
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From page 134... ...
There is ample anecdotal evidence of patients with no prior psychiatric illness who experience malaise, dysphoria, or outright clinical depression when starting treatment with beta-adrenergic antagonists, and central nervous system side effects from propranolol range in frequency from loo to over 70~o (Paykel et al., 1982~. Reported symptoms include depression, drowsiness, sleep disorders, and hallucinations.
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From page 135... ...
Small-airway dysfunction increases with age and can be observed in smokers of all ages (Enjeti et al., 1978~. Those observations have led to the recognition of the importance of peripheral lung structure and function in the evolution of lung aging or disease and to the focus for the last 15 years on studies of peripheral lung function in the evaluation of environmental exposures (Macklem 1972~.
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From page 136... ...
Not only Is there clear epidemiologic evidence that age and environmental factors, such as smoking, are associated with lo" of lung function, equally clear ~ an important correlation between Jung dysfunction and mortality from all causes (puhnonary and nonpulmonary)
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From page 137... ...
Despite a substantial body of information on the effects of aging on cardiovascular physiology, the extent to which the aged might be particularly vulnerable to the toxic effects of drugs, chemicals, and other environmental agents has received scant attention. The possibility of a difference in the response of the aged myocardium to cardiac glycosides, such as ouabain and digoxin, has been investigated in animals and humans (AIgeo et al., 1983~.
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From page 138... ...
The clinical observations related to doxorubicin suggest that other chemicals and environmental agents that produce free radicals might be associated with myocardial damage and that the effects might increase with age. Surprisingly, data on that point "d I ~ .
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From page 139... ...
for the study of aging, because it is genetically homogeneous and because it does not develop the obesity that occurs with advancing age in many rat strains. However, a major problem with the strain, as with most other rat strains, has been renal failure with advancing age, which precludes the study of normal aging processes in some of the rats by the age of 18 months and in many after the age of 24 months.
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From page 140... ...
Some environmental influences on immune function affect life span and therefore presumably affect susceptibility to disease or the aging processes themselves. Of the environmental factors, nutrition has a most dramatic effect on both immunity and life span in rodents.
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From page 141... ...
The striking increase in the morbidity and mortality associated with influenza in elderly people is a common clinical consequence of immune senescence. In addition to the 108s of cell-mediated immunity with age, the loss of thymic function leads to the dy~regulation of immune reactions.
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From page 142... ...
Environmental agents, such as ionizing racliation, pharmaceuticals, and cigarette smoking, have been shown to alter the age of menopause (i.e., ovarian failures (Chapman, 1983; Mattison, 1985; Mattison and Ross, 1983~. However, 60~o of all women do not experience remarkable physical or emotional symptoms associated with menopause, and of those who do, most have only minimal to moderate physical problems, including headaches and neckaches, hot flashes, fatigue, and feelings of emotional instability.
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From page 143... ...
Although a number of gradual and fairly predictable changes in sexual function occur with aging, they are often confounded by the effects of environmental agents. ROLE OF E:NVI:RONMENT IN BONE M1:TABOLISM AND VITAMIN D NUTRITION One of the major problems associated with aging is the loss of bone mass.
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From page 144... ...
However, because of the increased awareness that exposure to sunlight can cause skin cancer and dry and wrinkled skin, the elderly are often advised to corer their skin with clothing or a sunscreen before going outdoors. Those measures prevent not only the damaging effect of solar irradiation, but also the beneficial effect the production of vitamin D3 in the skin (MacLaughlin and Holick, 1985~.
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