title: Mitochondrial Metabolism in Aging Heart.
abstract: Altered mitochondrial metabolism is the underlying basis for the increased sensitivity in the aged heart to stress. The aged heart exhibits impaired metabolic flexibility, with a decreased capacity to oxidize fatty acids and enhanced dependence on glucose metabolism. Aging impairs mitochondrial oxidative phosphorylation, with a greater role played by the mitochondria located between the myofibrils, the interfibrillar mitochondria. With aging, there is a decrease in activity of complexes III and IV, which account for the decrease in respiration. Furthermore, aging decreases mitochondrial content among the myofibrils. The end result is that in the interfibrillar area, there is ≈50% decrease in mitochondrial function, affecting all substrates. The defective mitochondria persist in the aged heart, leading to enhanced oxidant production and oxidative injury and the activation of oxidant signaling for cell death. Aging defects in mitochondria represent new therapeutic targets, whether by manipulation of the mitochondrial proteome, modulation of electron transport, activation of biogenesis or mitophagy, or the regulation of mitochondrial fission and fusion. These mechanisms provide new ways to attenuate cardiac disease in elders by preemptive treatment of age-related defects, in contrast to the treatment of disease-induced dysfunction.
authors.affiliation: From the Division of Cardiology, Department of Medicine, Pauley Heart Center (E.J.L, Q.C.), Departments of Biochemistry and Molecular Biology and Physiology and Biophsyics (E.J.L.), Virginia Commonwealth University, Richmond, VA (E.J.L., Q.C.); Medical Service, McGuire Veterans Affairs Medical Center, Richmond, VA (E.J.L.); and Departments of Pharmacology (C.L.H.) and Medicine (E.J.L., C.L.H.), Center for Mitochondrial Disease (C.L.H.), Case Western Reserve University, School of Medicine, Cleveland, OH.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Lesnefsky
authors.affiliation: From the Division of Cardiology, Department of Medicine, Pauley Heart Center (E.J.L, Q.C.), Departments of Biochemistry and Molecular Biology and Physiology and Biophsyics (E.J.L.), Virginia Commonwealth University, Richmond, VA (E.J.L., Q.C.); Medical Service, McGuire Veterans Affairs Medical Center, Richmond, VA (E.J.L.); and Departments of Pharmacology (C.L.H.) and Medicine (E.J.L., C.L.H.), Center for Mitochondrial Disease (C.L.H.), Case Western Reserve University, School of Medicine, Cleveland, OH.
authors.forename: Qun
authors.initials: Q
authors.lastname: Chen
authors.affiliation: From the Division of Cardiology, Department of Medicine, Pauley Heart Center (E.J.L, Q.C.), Departments of Biochemistry and Molecular Biology and Physiology and Biophsyics (E.J.L.), Virginia Commonwealth University, Richmond, VA (E.J.L., Q.C.); Medical Service, McGuire Veterans Affairs Medical Center, Richmond, VA (E.J.L.); and Departments of Pharmacology (C.L.H.) and Medicine (E.J.L., C.L.H.), Center for Mitochondrial Disease (C.L.H.), Case Western Reserve University, School of Medicine, Cleveland, OH. charles.hoppel@case.edu.
authors.forename: Charles L
authors.initials: CL
authors.lastname: Hoppel
mesh_terms: D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D045222:Electron Transport Chain Complex Proteins / Q000235:genetics / Q000378:metabolism*; D006321:Heart / Q000254:growth & development* / Q000503:physiopathology; D006801:Humans; D008929:Mitochondria, Heart / Q000378:metabolism*; D001678:Organelle Biogenesis; D018384:Oxidative Stress
chemical_list: D045222:Electron Transport Chain Complex Proteins
keywords: cardiolipin; electron transport chain complex proteins; fatty acid oxidation complex; oxidative phosphorylation; reactive oxygen species