Decrease in oxidative phosphorylation with aging correlates with the aging phenotype

Abstract

The goal of the present study was to evaluate the implication of mitochondrial function in the age associated decrease in cardiac contractile function. Mitochondrial respiratory capacity was measured in permeabilized fibers from left ventricles of young and old rats from 3 different stains, presenting or not the aging phenotype. The Fisher 344 rats show severe age related pathology compare to the brown Norway rats. In contrast, hybrids Fisher 344 X Brown Norway showed a longer life expectancy and significantly fewer pathological lesions related to aging compared to the two other strains. A dramatic decrease of around 45% in coupled oxidative phosphorylation (OXPHOS) was observed in the old (24‐26 months) compared to the young (6 months) Fisher 344. The effect of aging on respiration was similar for complexes I, II, and IV, supporting either a decrease in mitochondrial content, an oxidative defect, or both with aging. The same trend, but without significant differences, was observed in cardiac fibers from the brown Norway, with a 15‐20% decrease in OXHPOS in the aged rats. The hybrids rats, which show better resistance to aging, do not have any loss of mitochondrial function. The severity of the age‐related pathology in the different strains correlates strongly with the presence of mitochondrial dysfunction. Our results suggest the importance mitochondrial defect in the deterioration of cardiac function during aging.