Late-in-life treadmill training rejuvenates autophagy, protein aggregate clearance, and function in mouse hearts.
Late-in-life treadmill training rejuvenates autophagy, protein aggregate clearance, and function in mouse hearts.
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DOI：
10.1111/acel.13467
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发表时间：
2021-10
期刊：
影响因子：
7.8
通讯作者：
Symons JD
中科院分区：
文献类型：
--
作者：
Cho JM;Park SK;Ghosh R;Ly K;Ramous C;Thompson L;Hansen M;Mattera MSLC;Pires KM;Ferhat M;Mookherjee S;Whitehead KJ;Carter K;Buffolo M;Boudina S;Symons JD
心脏衰老过程中蛋白质质量控制机制下降。这使得蛋白质聚集体和受损细胞器积累，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（例如心肌细胞）清除有缺陷的蛋白质和细胞器的过程。我们假设晚年的运动训练可以改善老年小鼠心脏与成年小鼠心脏中的自噬、蛋白质聚集物清除和功能失调。正如预期的那样，与 8 个月大（成年）小鼠相比，24 个月大的雄性 C57BL/6J 小鼠（老年）表现出心脏自噬体形成和蛋白质聚集体积累受到抑制、收缩和舒张功能障碍以及运动能力下降（所有 p < 0.05）。为了研究晚年运动训练的影响，额外的 21 个月大小鼠组（old-ETR）或没有（old-SED）完成了 3 个月的渐进阻力跑步机跑步计划。 24 个月时，与老 SED 小鼠相比，老 ETR 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 p < 0.05）。重要的是，自噬标记物的蛋白质表达表明，与老 SED 小鼠相比，老 ETR 小鼠心脏中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 p < 0.05）。这些数据提供了第一个证据，证明晚年开始的生理干预可以改善小鼠心脏的自噬通量、蛋白质聚集物清除和收缩性能。老年久坐小鼠表现出心脏功能下降：稳态自噬；自噬通量；蛋白质清除率；氧化还原平衡；线粒体质量；和功能。如果老年小鼠以适当的强度、频率和持续时间开始运动训练，这些与年龄相关的心脏干扰都会得到缓解。
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. Aged sedentary mice exhibit reduced cardiac: steady‐state autophagy; autophagic flux; protein clearance; redox balance; mitochondria quality; and function. If aged mice initiate exercise training at the proper intensity, frequency, and duration, each of these age‐associated cardiac disruptions is mitigated.
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影响因子：
20.1
作者：
Dai DF;Rabinovitch PS;Ungvari Z
通讯作者：
Ungvari Z
影响因子：
6.1
作者：
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通讯作者：
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DOI：
10.1093/gerona/glw168
发表时间：
2017-04-01
影响因子：
5.1
作者：
Ma, Li;Zhu, Jiang;Liu, Lixin
通讯作者：
Liu, Lixin
影响因子：
9.3
作者：
Dai, Dao-Fu;Rabinovitch, Peter S.
通讯作者：
Rabinovitch, Peter S.
影响因子：
7.8
作者：
Flynn JM;O'Leary MN;Zambataro CA;Academia EC;Presley MP;Garrett BJ;Zykovich A;Mooney SD;Strong R;Rosen CJ;Kapahi P;Nelson MD;Kennedy BK;Melov S
通讯作者：
Melov S