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

• Autor(a) principal: Cho, Jae Min
• Data de Publicação: 2021
• Outros Autores: Park, Seul-Ki, Ghosh, Rajeshwary, Ly, Kellsey, Ramous, Caroline, Thompson, Lauren, Hansen, Michele, Mattera, Maria Sara de Lima Coutinho [UNESP], Pires, Karla Maria, Ferhat, Maroua, Mookherjee, Sohom, Whitehead, Kevin J., Carter, Kandis, Buffolo, Márcio, Boudina, Sihem, Symons, J. David
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNESP
• Texto Completo: http://dx.doi.org/10.1111/acel.13467; http://hdl.handle.net/11449/222457
• topic: aging; cardiac function; exercise; protein aggregates

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.