MYOCARDIAL RESPONSE TO EXERCISE DURING SENESCENCE

拟议工作的总体目标是通过以下方式界定这些机制 运动训练会改变衰老大鼠的心脏功能。 在衰老的大鼠中，离体心的松弛受损 这与钙离子转运速率的降低有关 肌浆网的钙泵(CaATPase)。耐力 运动训练提高老年大鼠钙转运速率 心脏SR伴随着孤立性心动过速 心肌。我们的具体目标是确定 老年大鼠心脏肌浆网钙转运减弱的基础 评估运动训练对这些机制的影响。这个 离体乳头肌和乳头肌的等长收缩特性 将评估大鼠的最大耗氧量(最大容量) 与这些研究相结合。将通过以下方式实现这一目标 CAATPase特异性mRNA含量的测定 CaATPase蛋白含量和CaATPase合成速率 心脏中的蛋白质通过重组DNA、免疫沉淀和 分别介绍了标记技术。膜水平上的因素 对钙转运过程的重要性将在 利用多种生化和抗体技术分离心脏SR。 停止训练后，运动诱发的回归 改善固有收缩性能和钙转运 在心里会下定决心。这项运动对 与年龄相关的固有收缩性能下降的速度和 心脏肌浆网的钙转运将被解决。药剂的作用 而已知的调节心脏钙运动的条件将是 在分离的心肌中进行监测。最后，磷脂蛋白的作用 在心脏SR中对钙离子的运输和肌肉力学都会产生影响 下定决心。这些研究将使我们深入了解细胞机制。 衰老过程中心脏功能减退的潜在原因 通过运动训练进行改进，从而提高运动质量 生活。

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.