MassIVE MSV000084961

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

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Description

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. [doi:10.25345/C5MD6H] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: ss-31, aging, cardiac aging, mitochondrial function, elamipretide, mCAT, catalase

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Principal Investigators:
(in alphabetical order) 		Peter S. Rabinovitch, University of Washington, United States
Submitting User: nbasisty
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