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 C-13 labeled palmitate, and either C-13 labeled lactate or C-13 glucose. C-13-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. (c) 2005 Elsevier Ltd. All rights reserved