Aging in Today's Environment (1987) / Chapter Skim
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7 Model Systems for the Evaluation of Toxic Agents Affecting Aging or Age-Related Diseases
7 Model Systems for the Evaluation of Toxic Agents Affecting Aging or Age-Related Diseases
Pages 145-161
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From page 145... ...
In the first phase of the development of short-term screening tests, appropriate mode! systems were used to obtain information on the various mechanisms that produce genetic lesions and to identify the types of genotoxic agents that would produce gene mutations, chromosomal aberrations, and aneuploidy.
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From page 146... ...
systems to evaluate the effects of environmental chemicals on aging is first, to identify short-term tests that can be used to screen environmental chern~cals for their potential to affect aging processes or age-associated diseases; second, to screen chemicals; and third, to test those chemicals that had positive results in short-term tests in mammalian model systems to develop a data base for predicting human responses. CONSIDERATIONS IN CHOOSING AND DESIGNING MODEL SYSTEMS The general lack of information about the fundamental nature of aging processes poses problems for risk assessment of potential environmental agents that promote aging.
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From page 147... ...
, who compared the longevity characteristics of conventionally mainta~ned Wistar rats with those of Wistar rats kept specific-pathogenfree in a barrier facility. Both the median length of life and the life span of the specific-pathogen-free rats were markedly greater.
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From page 148... ...
He found that over 65%0 of conventionally housed female C3H/HeJ mice had mammary tumors at the age of 400 days, whereas fewer than logo of the mice protected from the noise, odors, and other stressors common to conventional anneal facilities had these tumors at the same age. Riley related that finding to the difference in plasma corticosterone concentrations, which were 15~500 ng/m!
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From page 149... ...
Many fundamental physiologic and molecular processes in humans are also present in many invertebrates ~d other vertebrates, and there is no a priori reason to expect aging processes to be different. Each model system must be approached on its own merits, and validity assessment must be based on background information on the disease state, the mode!
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From page 150... ...
. Established, serially passaged cultures with relatively reproducible cycles of growth in early phases, but with limited replicative life span, and with a genetic makeup reflecting that of the donor animal.
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From page 151... ...
Considerable progress has been made in the culture of other cell types, including epidermal keratinocytes, epidermal melanocytes, lenticular epitheliai cells, renal epithelial cells, chondrocytes, arterial and venous endothelial cells, vascular smooth muscle cells, skeletal muscle satellite cells and myoblasts, erythroid stem cells, myeloid stem cells, T arid B lymphocytes, glial cells, and retinal epithelial cells. Much of this progress has been associated with the improved characterizations of optimal growth media, especially of subsets of growth factors.
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From page 152... ...
Life span has also been the end point most often assayed in invertebrates, although other end points, such as accumulation of lipofusc~n and the end of reproductive ability, have also been used. Because of their short life spans, relative ease of use, and relatively low cost, invertebrate organisms will likely be important ~ the initial phases of a test system to detect environmental toxins that might affect aging or age-related diseases.
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From page 153... ...
The somatic cells of adult nematodes are all postreplicative; mean life spans are a few weeks; and kinetics of death display the Gompertzian increase in mortality seen in higher metazoans. A variety of morphologic, behavioral, physiologic, and molecular changes occur over the life span of the nematode (Johnson and Simpson, 1985~; some uremic changes observed in the mammalian aging processes, such as loss of general motor ability (Bolanowski et al., 1981; Johnson, 1987)
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From page 154... ...
D melanogaster, the most widely studied invertebrate species, has been the most widely used in aging research (Baker et al., 1985~.
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From page 155... ...
crassa and P anserine have been widely exploited both in aging research and in classical and molecular genetic analyses.
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From page 156... ...
Prominent biochemists and metabolic physiologists cornrnonly draw conclusions about age-related changes in a biochemical pros cess on the basis of a study limited to 2-month-old and ~month-old rats in a strain with a life span of 48 months. Although such studies are of value, a broader range of ages should be studied if the influence of age on biochemical activity is to be aclequately defined.
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From page 157... ...
Restricting the rat strain to 60% of the ad libitum food intake prevents the pros gressive chronic nephropathy. The National Institute on Aging is developing Brown-Norway, Fischer 344 Fat hybrids for the purpose of partially circumventing chronic nephropathy.
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From page 158... ...
Inbred strains often suffer from a single major dmease process (e.g., cancer of the liver or chronic nephropathy) , and the presence of this major disease process in most if not all the animals complicates gerontologic interpretation.
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From page 159... ...
Epidemiologic Models The expression "experiments of nature" refers to contrasts in the exposure of human populations to toxic agents that provide an opportunity to assess the impact of toxic exposures on the risk of disease and death in the human population. Many reports of acute and chronic releases of toxic agents into the human environment gave rise to marked contrasts In toxic exposures and disease outcomes.
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From page 160... ...
It appears, therefore, that the radiation effect manifested as lung, breast, and other solid tumors is observed only in people who have reached the age range normally associated with the incidence of cancer. LIFESPAN MODULATION BY DRUG T1lEATMI:NT The effects of toxic agents on aging or aging processes have not been widely studied (Schneider and Reed, 1985~.
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From page 161... ...
No single drug treatment or dietary additive has been reliably shown to extend life span in any organism.
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