The overall aim of the proposed work is to delineate the mechanisms by which exercise training alters the function of the heart in senescent rats. In the senescent rat there is an impaired relaxation of the isolated heart which is associated with a diminished rate of calcium transport by the calcium pump (CaATPase) of the sarcoplasmic reticulum (SR). Endurance exercise training of old rats improves the rate of calcium transport by cardiac SR which is accompanied by a faster relaxation of the isolated heart muscle. Our specific objective is to determine the mechanisms underlying the diminished calcium transport of cardiac SR from old rats and to evaluate the impact exercise training has on those mechanisms. The isometric contractile properties of the isolated papillary muscle and maximal oxygen consumption (maximal capacity) of the rats will be assessed in conjunction with these studies. This objective will be approached by determining the content of the mRNA specific for the CaATPase, total content of the CaATPase protein, and the synthesis rate of the CaATPase protein in the heart through recombinant DNA, immunoprecipitation, and labelling techniques, respectively. Factors at the level of the membrane important to the calcium transport process will be determined in the isolated cardiac SR using a variety of biochemical and antibody techniques. After the cessation of training, the regression of the exercise-induced improvement of the intrinsic contractile properties and calcium transport in the heart will be determined. The impact that exercise has on the aging-related rate of decline in intrinsic contractile performance and calcium transport by cardiac SR will be addressed. The effect of agents and conditions known to modulate calcium movements in the heart will be monitored in isolated cardiac muscle. Finally, the role that phospholamban in cardiac SR has on calcium transport and muscle mechanics will be determined. These studies will give insight into the cellular mechanisms underlying the diminished cardiac function during senescence and the improvement by exercise training which leads to an enhanced quality of life.
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