Late-in-life treadmill training rejuvenates autophagy, protein aggregate clearance, and function in mouse hearts

Author(s):Show less -

Cho, Jae Min ^[1] ; Park, Seul-Ki ^[1] ; Ghosh, Rajeshwary ^[1] ; Ly, Kellsey ^[1] ; Ramous, Caroline ^[1] ; Thompson, Lauren ^[1] ; Hansen, Michele ^[1] ; Mattera, Maria Sara de Lima Coutinho ^[2] ; Pires, Karla Maria ^[1] ; Ferhat, Maroua ^[1] ; Mookherjee, Sohom ^[1] ; Whitehead, Kevin J. ^{[3, 4, 5]} ; Carter, Kandis ^[3] ; Buffolo, Marcio ^[1] ; Boudina, Sihem ^{[3, 1]} ; Symons, J. David ^{[3, 1]}

Affiliation

^[1] Univ Utah, Nutr & Integrat Physiol, Salt Lake City, UT 84112 - USA

^[2] Sao Paulo State Univ, Sch Dent, Aracatuba - Brazil

^[3] Univ Utah, Mol Med Program, Salt Lake City, UT - USA

^[4] Univ Utah, Div Cardiovasc Med & Pediat Cardiol, Salt Lake City, UT - USA

^[5] Univ Utah, George E Wahlen VA Med Ctr, Salt Lake City, UT - USA

• Document type: Journal article
• Source: AGING CELL; v. 20, n. 10 SEP 2021.
• Web of Science Citations: 0

Abstract

Protein quality control mechanisms decline during the process of cardiac aging. This enables the accumulation of protein aggregates and damaged organelles that contribute to age-associated cardiac dysfunction. Macroautophagy is the process by which post-mitotic cells such as cardiomyocytes clear defective proteins and organelles. We hypothesized that late-in-life exercise training improves autophagy, protein aggregate clearance, and function that is otherwise dysregulated in hearts from old vs. adult mice. As expected, 24-month-old male C57BL/6J mice (old) exhibited repressed autophagosome formation and protein aggregate accumulation in the heart, systolic and diastolic dysfunction, and reduced exercise capacity vs. 8-month-old (adult) mice (all p < 0.05). To investigate the influence of late-in-life exercise training, additional cohorts of 21-month-old mice did (old-ETR) or did not (old-SED) complete a 3-month progressive resistance treadmill running program. Body composition, exercise capacity, and soleus muscle citrate synthase activity improved in old-ETR vs. old-SED mice at 24 months (all p < 0.05). Importantly, protein expression of autophagy markers indicate trafficking of the autophagosome to the lysosome increased, protein aggregate clearance improved, and overall function was enhanced (all p < 0.05) in hearts from old-ETR vs. old-SED mice. These data provide the first evidence that a physiological intervention initiated late-in-life improves autophagic flux, protein aggregate clearance, and contractile performance in mouse hearts. (AU)

• FAPESP's process: 17/13817-6 - Ceramide produces vascular dysfunction via autonomous actions within the endothelium
• Grantee: Maria Sara de Lima Coutinho Mattera
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate