当前位置: X-MOL 学术Aging Cell › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Late-in-life treadmill training rejuvenates autophagy, protein aggregate clearance, and function in mouse hearts
Aging Cell ( IF 8.0 ) Pub Date : 2021-09-23 , DOI: 10.1111/acel.13467
Jae Min Cho 1 , Seul-Ki Park 1 , Rajeshwary Ghosh 1 , Kellsey Ly 1 , Caroline Ramous 1 , Lauren Thompson 1 , Michele Hansen 1 , Maria Sara de Lima Coutinho Mattera 2 , Karla Maria Pires 1 , Maroua Ferhat 1 , Sohom Mookherjee 1 , Kevin J Whitehead 3, 4, 5 , Kandis Carter 3 , Márcio Buffolo 1 , Sihem Boudina 1, 3 , J David Symons 1, 3
Affiliation  

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 < 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 < 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 < 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.

中文翻译:

晚年跑步机训练使小鼠心脏中的自噬、蛋白质聚集体清除和功能恢复活力

蛋白质质量控​​制机制在心脏衰老过程中下降。这使得蛋白质聚集体和受损细胞器的积累成为可能,从而导致与年龄相关的心脏功能障碍。巨自噬是有丝分裂后细胞(如心肌细胞)清除有缺陷的蛋白质和细胞器的过程。我们假设晚年运动训练可以改善自噬、蛋白质聚集体清除和功能,否则这些功能会在老年小鼠和成年小鼠的心脏中失调。正如所料,24 个月大的雄性 C57BL/6J 小鼠(老)与 8 个月大(成年)小鼠(所有< 0.05)。为了研究晚年运动训练的影响,另外一组 21 个月大的小鼠完成了(老 ETR)或没有(老 SED)3 个月的渐进式阻力跑步机跑步计划。在 24 个月时,老年 ETR 与老年 SED 小鼠的身体成分、运动能力和比目鱼肌柠檬酸合酶活性有所改善(所有 < 0.05)。重要的是,自噬标志物的蛋白质表达表明自噬体向溶酶体的运输增加,蛋白质聚集体清除率提高,整体功能增强(所有< 0.05) 在老 ETR 与老 SED 小鼠的心脏中。这些数据提供了第一个证据,表明生命后期开始的生理干预可以改善小鼠心脏的自噬通量、蛋白质聚集体清除和收缩性能。
更新日期:2021-10-17
down
wechat
bug