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

• DOI: 10.7554/elife.55513
• Publication Date: 2020-07-10T12:00:22Z
• Authors: 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; Gennifer Merrihew; Lu Wang; Yongping Yue; Dongsheng Duan; Henk L Granzier; Hazel H Szeto; Wei-Jun Qian; David Marcinek; Michael J MacCoss; Peter Rabinovitch
• Keywords: 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

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.