Metabolic remodeling in the aging heart.
The aim of this study was to investigate the effects of aging on the profile of myocardial substrate utilization and cardiac function using a physiological profile of substrates. Hearts from 6-, 15- and 24-month male Wistar rats were perfused in the isovolumic Langendorff mode, with physiological concentrations of 13C labeled palmitate, and either 13C labeled lactate or 13C glucose. 13C-NMR glutamate isotopomer analysis was performed to determine the contribution of the different substrates to oxidative metabolism. Palmitate oxidation was significantly increased and lactate oxidation depressed in the 24-month old, senescent hearts compared to the mature 6-month hearts. This metabolic remodeling was paralleled with a marked decline in cardiac function and efficiency. These results highlight that adaptations in substrate utilization occur during senescence and may contribute to the age-related increase in the incidence of heart failure.
Sample
Jessica
J
Department of Biological Sciences, The University of Hull, Cottingham Road, Kingston-upon-Hull HU6 7RX, UK.
Cleland
John G F
JG
Seymour
Anne-Marie L
AM
D000375:Aging / Q000502:physiology*; D000818:Animals; D002950:Citrate (si)-Synthase / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006321:Heart / Q000502:physiology*; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D019308:Palmitic Acid / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020257:Ventricular Remodeling / Q000502:physiology*
D005227:Fatty Acids; D019308:Palmitic Acid; D019344:Lactic Acid; D007770:L-Lactate Dehydrogenase; D002950:Citrate (si)-Synthase; D005947:Glucose