Late-life restoration of mitochondrial function reverses cardiac dysfunction in old mice release_477tyhloc5b7dfppwwp5s6rtzi

by Ying Ann Chiao, Huiliang Zhang, Mariya Sweetwyne, Jeremy Whitson, Ying Sonia Ting, Nathan Basisty, Lindsay K Pino, Ellen Quarles, Ngoc-Han Nguyen, Matthew D Campbell, Tong Zhang, Matthew J Gaffrey (+10 others)

Published in eLife by eLife Sciences Publications, Ltd.

2020  

Abstract

Diastolic dysfunction is a prominent feature of cardiac aging in both mice and humans. We show here that 8-week treatment of old mice with the mitochondrial targeted peptide SS-31 (elamipretide) can substantially reverse this deficit. SS-31 normalized the increase in proton leak and reduced mitochondrial ROS in cardiomyocytes from old mice, accompanied by reduced protein oxidation and a shift towards a more reduced protein thiol redox state in old hearts. Improved diastolic function was concordant with increased phosphorylation of cMyBP-C Ser282 but was independent of titin isoform shift. Late-life viral expression of mitochondrial-targeted catalase (mCAT) produced similar functional benefits in old mice and SS-31 did not improve cardiac function of old mCAT mice, implicating normalizing mitochondrial oxidative stress as an overlapping mechanism. These results demonstrate that pre-existing cardiac aging phenotypes can be reversed by targeting mitochondrial dysfunction and implicate mitochondrial energetics and redox signaling as therapeutic targets for cardiac aging.
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Date   2020-07-10
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ISSN-L:  2050-084X
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