REGULATION OF ENERGY METABOLISM IN AGING AND DISEASE--CARDIOVASCULAR SYSTEM

该项目研究了老年人和老年人的线粒体功能， 在病理状态下， 线粒体可能损害组织存活。 (1)我们把重点放在 线粒体Ca 2+离子稳态改变 以及氧化磷酸化的潜力。 我们已经扩大了我们的 先前对心肌病叙利亚人心肌细胞的研究 仓鼠。 在失败点研究，这些心脏表现较差 也不能完全激活丙酮酸脱氢酶， 在健康的心脏中。 去年，我们把这一点与一个失败联系在一起， 肌病细胞线粒体内游离钙（[Ca 2 +m]）升高 动物，当[Ca 2 +]m在单个心肌细胞中进行研究时， 进行电起搏治疗。 今年我们展示了 [Ca 2 +]m对增加的反应减弱的可能原因 心肌病患者的电刺激频率是 在胞质游离Ca 2+中产生较小的收缩瞬变 ([Ca2+]c）来自衰竭心脏的肌细胞。 (2)我们延长 [Ca ~（2+）]m对频率依赖性的研究 电刺激，以分离由于β-肾上腺素能 频率刺激。 此外，我们还利用了 线粒体解偶联剂提供一个独立的 证实了我们的发现，即线粒体Ca 2+梯度可能 是积极的或消极的，这取决于细胞刺激的程度。

This project examines mitochondrial functioning in old age and in pathological states in which decreased energy transduction by mitochondria may compromise tissue survival. (1) We have focused this year on the relation between altered mitochondrial Ca2+ ion homeostasis and the potential for oxidative phosphorylation. We have extended our previous work on cardiac myocytes from the cardiomyopathic Syrian hamster. Studied at the point of failure, these hearts perform less work and also fail to activate pyruvate dehydrogenase as completely as in healthy hearts. In the previous year we tied this to a failure to elevate intramitochondrial free Ca2+ ([Ca2+m) in cells from myopathic animals, when [Ca2+]m was studied in individual cardiac myocytes subjected to an electrical pacing regimen. This year we showed that the likely cause of the diminished response of [Ca2+]m to increased frequency of electrical stimulation in the cardiomyopathic is the generation of smaller systolic transients in cytosolic free Ca2+ ([Ca2+]c) in myocytes from the failing hearts. (2) We have extended the previous year's studies on the dependence of [Ca2+]m upon frequency of electrical stimulation, to separate an effect due to beta-adrenergic stimulation from that of frequency. Further, we have used the effect of mitochondrial uncoupling agents to provide an independent verification of our finding that the mitochondrial Ca2+ gradient may be positive or negative, depending upon the degree of cell stimulation.