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： 运动训练改变了衰老大鼠的心脏功能。 衰老大鼠离体心脏舒张功能受损 这与钙转运速率的降低有关， 肌浆网（SR）的钙泵（CaATPase）。 耐力 老年大鼠的运动训练通过以下方式提高钙转运速率： 心脏SR，伴随着孤立的 心肌 我们的具体目标是确定 老年大鼠心脏SR钙转运减少的基础， 评估运动训练对这些机制的影响。 的 离体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 结合这些研究。 为实现这一目标， 测定CaATP酶特异性mRNA的含量，总 CaATPase蛋白质含量及CaATPase合成速率 通过重组DNA，免疫沉淀， 标签技术。 膜水平的因素 重要的钙转运过程将确定在 使用各种生化和抗体技术分离心脏SR。 停止训练后，运动诱发的 改善固有收缩特性和钙转运 心，将决定。 运动对 衰老相关的内在收缩性能下降率， 将讨论心脏SR的钙转运。 药剂的效果 并且已知调节心脏中钙运动的条件将是 在离体心肌中监测。 最后，受磷蛋白 在心脏SR对钙转运和肌肉力学的影响 测定 这些研究将有助于深入了解细胞机制 衰老期间心脏功能下降的潜在原因， 通过运动训练改善，从而提高 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.