title: Changes in the mitochondrial function and in the efficiency of energy transfer pathways during cardiomyocyte aging.
abstract: 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.
authors.affiliation: Laboratory of Bioenergetics, National Institute of Chemical Physics and Biophysics, Akadeemia tee 23, 12618, Tallinn, Estonia. kersti.tepp@kbfi.ee.
authors.forename: Kersti
authors.identifier: http://orcid.org/0000-0001-7367-6632
authors.initials: K
authors.lastname: Tepp
authors.affiliation: Laboratory of Bioenergetics, National Institute of Chemical Physics and Biophysics, Akadeemia tee 23, 12618, Tallinn, Estonia.
authors.forename: Marju
authors.initials: M
authors.lastname: Puurand
authors.affiliation: Laboratory of Bioenergetics, National Institute of Chemical Physics and Biophysics, Akadeemia tee 23, 12618, Tallinn, Estonia.
authors.forename: Natalja
authors.initials: N
authors.lastname: Timohhina
authors.affiliation: Laboratory of Chemical Physics, National Institute of Chemical Physics and Biophysics, Tallinn, Estonia.
authors.forename: Jasper
authors.initials: J
authors.lastname: Adamson
authors.affiliation: Laboratory of Bioenergetics, National Institute of Chemical Physics and Biophysics, Akadeemia tee 23, 12618, Tallinn, Estonia.
authors.forename: Aleksandr
authors.initials: A
authors.lastname: Klepinin
authors.affiliation: Laboratory of Bioenergetics, National Institute of Chemical Physics and Biophysics, Akadeemia tee 23, 12618, Tallinn, Estonia.
authors.forename: Laura
authors.initials: L
authors.lastname: Truu
authors.affiliation: Laboratory of Bioenergetics, National Institute of Chemical Physics and Biophysics, Akadeemia tee 23, 12618, Tallinn, Estonia.
authors.forename: Igor
authors.initials: I
authors.lastname: Shevchuk
authors.affiliation: Laboratory of Bioenergetics, National Institute of Chemical Physics and Biophysics, Akadeemia tee 23, 12618, Tallinn, Estonia.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Chekulayev
authors.affiliation: Laboratory of Bioenergetics, National Institute of Chemical Physics and Biophysics, Akadeemia tee 23, 12618, Tallinn, Estonia.|School of Natural Sciences and Health, Tallinn University, Tallinn, Estonia.
authors.forename: Tuuli
authors.initials: T
authors.lastname: Kaambre
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D016922:Cellular Senescence / Q000502:physiology; D006019:Glycolysis / Q000502:physiology*; D008929:Mitochondria, Heart / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D051381:Rats; D017208:Rats, Wistar
keywords: Adenylate kinase; Aging; Cardiomyocytes; Creatine kinase; Energy metabolism; Mitochondria