Changes in the myocardial energetics associated with aging-reductions in creatine phosphate/ATP ratio, total creatine, and ATP-mirror changes observed in failing hearts compared to healthy controls. Similarly, both aging and heart failure are associated with significant reductions in cardiac performance and maximal left ventricular cardiac power output compared with young healthy individuals. Based on these observations, we hypothesize that reductions in the concentrations of cytoplasmic adenine nucleotide, creatine, and phosphate pools that occur with aging impair the myocardial capacity to synthesize ATP at physiological free energy levels and that the resulting changes to myocardial energetic status impair the mechanical pumping ability of the heart. The purpose of this study is to test these hypotheses using an age-structured population model for myocardial metabolism in the adult female population and to determine the potential impact of reductions in key myocardial metabolite pools in causing metabolic/energetic and cardiac mechanical dysfunction associated with aging. To test these hypotheses, we developed a population model for myocardial energetics to predict myocardial ATP, ADP, creatine phosphate, creatine, and inorganic phosphate concentrations as functions of cardiac work and age in the adult female population. Model predictions support our hypotheses and are consistent with previous experimental observations. The major findings provide a novel, to our knowledge, theoretical and computational framework for further probing complex relationships between the energetics and performance of the heart with aging.

中文翻译：

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心脏代谢限制导致心脏老化性能下降

与健康对照相比，在衰竭心脏中观察到的与磷酸肌酸/ATP 比率、总肌酸和 ATP 镜像变化的衰老降低相关的心肌能量学变化。类似地，与年轻健康个体相比，衰老和心力衰竭都与心脏性能和最大左心室心脏功率输出显着降低有关。基于这些观察，我们假设随着衰老发生的细胞质腺嘌呤核苷酸、肌酸和磷酸盐浓度的降低会损害心肌在生理自由能水平合成 ATP 的能力，并且由此产生的心肌能量状态的变化会损害机械心脏的泵血能力。本研究的目的是使用年龄结构的成年女性人群心肌代谢模型来检验这些假设，并确定关键心肌代谢物库减少对导致与衰老相关的代谢/能量和心脏机械功能障碍的潜在影响. 为了验证这些假设，我们开发了一个心肌能量学群体模型，以预测成年女性人群中作为心脏功和年龄的函数的心肌 ATP、ADP、磷酸肌酸、肌酸和无机磷酸盐浓度。模型预测支持我们的假设并且与之前的实验观察一致。据我们所知，这些主要发现提供了一种新颖的