Tepp Kersti, Puurand Marju, Timohhina Natalja, Adamson Jasper, Klepinin Aleksandr, Truu Laura, Shevchuk Igor, Chekulayev Vladimir, Kaambre Tuuli
Laboratory of Bioenergetics, National Institute of Chemical Physics and Biophysics, Akadeemia tee 23, 12618, Tallinn, Estonia.
Laboratory of Chemical Physics, National Institute of Chemical Physics and Biophysics, Tallinn, Estonia.
Mol Cell Biochem. 2017 Aug;432(1-2):141-158. doi: 10.1007/s11010-017-3005-1. Epub 2017 Mar 14.
The role of mitochondria in alterations that take place in the muscle cell during healthy aging is a matter of debate during recent years. Most of the studies in bioenergetics have a focus on the model of isolated mitochondria, while changes in the crosstalk between working myofibrils and mitochondria in senescent cardiomyocytes have been less studied. The aim of our research was to investigate the modifications in the highly regulated ATP production and energy transfer systems in heart cells in old rat cardiomyocytes. The results of our work demonstrated alterations in the diffusion restrictions of energy metabolites, manifested by changes in the apparent Michaelis-Menten constant of mitochondria to exogenous ADP. The creatine kinase (CK) phosphotransfer pathway efficiency declines significantly in senescence. The ability of creatine to stimulate OXPHOS as well as to increase the affinity of mitochondria for ADP is falling and the most critical decline is already in the 1-year group (middle-age model in rats). Also, a moderate decrease in the adenylate kinase phosphotransfer system was detected. The importance of glycolysis increases in senescence, while the hexokinase activity does not change during healthy aging. The main result of our study is that the decline in the heart muscle performance is not caused by the changes in the respiratory chain complexes activity but mainly by the decrease in the energy transfer efficiency, especially by the CK pathway.
近年来，线粒体在健康衰老过程中肌肉细胞发生的变化中所起的作用一直是个有争议的问题。生物能量学的大多数研究都集中在分离线粒体的模型上，而衰老心肌细胞中工作肌原纤维与线粒体之间相互作用的变化则研究较少。我们研究的目的是调查老年大鼠心肌细胞中高度调节的ATP生成和能量转移系统的变化。我们的研究结果表明能量代谢物的扩散限制发生了改变，表现为线粒体对外源性ADP的表观米氏常数的变化。肌酸激酶（CK）磷酸转移途径的效率在衰老过程中显著下降。肌酸刺激氧化磷酸化以及增加线粒体对ADP亲和力的能力正在下降，最关键的下降已经出现在1年组（大鼠中年模型）。此外，还检测到腺苷酸激酶磷酸转移系统有适度下降。糖酵解的重要性在衰老过程中增加，而己糖激酶活性在健康衰老过程中没有变化。我们研究的主要结果是，心肌性能的下降不是由呼吸链复合物活性的变化引起的，而是主要由能量转移效率的降低引起的，尤其是由CK途径引起的。
