First Author | Chiao YA | Year | 2020 |
Journal | Elife | Volume | 9 |
PubMed ID | 32648542 | Mgi Jnum | J:302814 |
Mgi Id | MGI:6445148 | Doi | 10.7554/eLife.55513 |
Citation | Chiao YA, et al. (2020) Late-life restoration of mitochondrial function reverses cardiac dysfunction in old mice. Elife 9:e55513 |
abstractText | 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. |