The primary objective of this proposal is to compare the effects of chronic dehydroepiandrosterone (DHEA) administration and caloric undernutrition (CU) in respect to survivorship, tumor incidence and age-related histopathology in both a mouse and a rat model system of aging. An additional objective will be to assess the utility of age-related functional deficits and biochemical changes as indicative measurements of the rate of aging in populations subject to experimental regimens which may alter the natural rate of aging. Specifically, C57B1/6J female mice and Sprague-Dawley male rats will be divided into three groups: ad libitum feeding, calorically undernourished (60 % of ad libitum) and DHEA treated (0.3 to 0.4 % by weight of diet). Survivorhsip, tumor incidence and age related histopathology will be determined in each group. Both terminal biomarkers of aging (serial sacrifice for pathology, mitogenic response, minimum oxygen consumption and sister chromatid exchange) and non-terminal biomarkers of aging (proteinuria, passive avoidance latency and autoimmunity) will be determined periodically to ascertain which are the best indicators of altered rates of aging, the objective measurement of which is survivorship. DHEA treatment shares with CU a number of important effects, namely, anti-obesity, anti-cancer and anti-autoimmune effects. This proposal will determine whether DHEA has a beneficial effect on survivorship as has been previously demonstrated with CU. Valuable information will also be gained regarding the utility of biomarkers of aging as predictors of altered rates of aging.
| Pashko, L L; Fairman, D K; Schwartz, A G (1986) Inhibition of proteinuria development in aging Sprague-Dawley rats and C57BL/6 mice by long-term treatment with dehydroepiandrosterone. J Gerontol 41:433-8 |
| Whitcomb, J M; Schwartz, A G (1985) Dehydroepiandrosterone and 16 alpha-Br-epiandrosterone inhibit 12-O-tetradecanoylphorbol-13-acetate stimulation of superoxide radical production by human polymorphonuclear leukocytes. Carcinogenesis 6:333-5 |
