The Immunodeficiency of aging and Down's Syndrome (DS) are due to developing defects in lymphoid cells which present their proliferative responses to an immunogen. A number of features of DS suggest that it may serve, at least in part, as a model for accelerated aging in human, qualifying perhaps as front runner among the so-called progeroid syndromes. Lifespan is clearly diminished in DS. By 40 years pathologic charges characteristic of Alzheimer's disease are almost universally observed in DS. Since most immunologic investigations have been limited to stimulus-response experiments, the objective of this study is to investigate into basic biochemical and nutritional factors priming the immuno-deficiency of DS and aging. The response of lymphocytes to immunogen may be measured as incorporation of (3H)-thymidine (TdR) into replicating DNA while the stimulated cell undergoes blastogenesis. A large number of biochemical events must supervene between the initial stimulus and the final responses. This study proposes to test the following hypothesis: Hypothesis I. Lymphocytes from DS patients show a decreased response to PHA as measured by continuous 3H-TdR incorporation. They are defective in mitochondrial production of ATP; Hypothesis II. Mitochondria isolated from DS patients and normal aged controls are defective in respiratory rate; Hypothesis III. Mitochondria isolated from DS patients and normal aged humans are defective in trace element contents; Hypothesis IV. Kinetic experiments using pharmacological agents: To test whether cAMP level changes would bring about 4 better immune response in DS and the aged lymphocytes; Hypothesis V. A longitudinal 4 year analysis: To test which of the failing immune functional and/or nutritional parameters are the most important in terms of lifespan and disease expectancy. Students under the Minority Biomedical Research Support (MBRS) Program will be motivated to pursue their careers in geriatric medicine and health care. They will not only receive training in laboratory skills of biochemistry, nutrition and immunology but will also obtain clinical, social and practical nutritional counseling experience as they conduct studies on normal young and aged humans and DS patients. Moveover, these findings will eventually help to prevent or to meliorate immuno-deficiency of DS patients and aged humans.
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