Late-life restoration of mitochondrial function reverses cardiac dysfunction in old mice

Male Aging Heart Diseases QH301-705.5 Science aging Q R Mitochondria mitochondria Mice, Inbred C57BL Mice Oxidative Stress oxidative stress Medicine Animals diastolic dysfunction Female cardiac function Biology (General) Human Biology and Medicine Energy Metabolism Oligopeptides Oxidation-Reduction
DOI: 10.7554/elife.55513 Publication Date: 2020-07-10T12:00:22Z
ABSTRACT
Diastolic dysfunction is a prominent feature of cardiac aging in both mice and humans. We show here that 8-week treatment old with the mitochondrial targeted peptide SS-31 (elamipretide) can substantially reverse this deficit. normalized increase proton leak reduced ROS cardiomyocytes from mice, accompanied by protein oxidation shift towards more thiol redox state hearts. Improved diastolic function was concordant increased phosphorylation cMyBP-C Ser282 but independent titin isoform shift. Late-life viral expression mitochondrial-targeted catalase (mCAT) produced similar functional benefits did not improve mCAT implicating normalizing oxidative stress as an overlapping mechanism. These results demonstrate pre-existing phenotypes be reversed targeting implicate energetics signaling therapeutic targets for aging.
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