Autophagy and mitophagy flux in young and aged skeletal muscle following chronic contractile activity
Autophagy and mitophagy flux in young and aged skeletal muscle following chronic contractile activity
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DOI：
10.1113/jp275998
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发表时间：
2018-08-15
影响因子：
5.5
通讯作者：
Hood, David A.
中科院分区：
文献类型：
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作者：
Carter, Heather N.;Kim, Yuho;Hood, David A.
随着年龄的增长，骨骼肌线粒体质量出现缺陷。维持健康线粒体池的核心是通过线粒体自噬去除功能失调的细胞器。关于线粒体自噬如何随着衰老和长期运动而改变，人们知之甚少。我们在年轻和老年大鼠肌肉慢性收缩活动（CCA）后使用秋水仙碱治疗体内评估了线粒体自噬通量。 CCA 在年轻肌肉中引发线粒体生物发生，但在老年肌肉中反应减弱。衰老肌肉中的线粒体自噬通量较高，并且与线粒体自噬受体和上游转录调节因子的表达增强相关。 CCA 降低了两个年龄组的线粒体自噬通量，表明细胞器质量有所改善。 CCA 还减少了衰老肌肉中明显的 TFEB 过度表达，这可能促进了年龄诱导的溶酶体标记物的增加。因此，衰老的肌肉具有较高的自噬和线粒体自噬驱动力，这可能导致随年龄增长观察到的细胞器含量下降，但可能有助于维持线粒体质量。 CCA 可以改善细胞器的完整性并减少线粒体自噬，这表明长期锻炼是改善老年人群肌肉质量的一种方式。
Skeletal muscle exhibits deficits in mitochondrial quality with age. Central to the maintenance of a healthy mitochondrial pool is the removal of dysfunctional organelles via mitophagy. Little is known on how mitophagy is altered with ageing and chronic exercise. We assessed mitophagy flux using colchicine treatment in vivo following chronic contractile activity (CCA) of muscle in young and aged rats. CCA evoked mitochondrial biogenesis in young muscle, with an attenuated response in aged muscle. Mitophagy flux was higher in aged muscle and was correlated with the enhanced expression of mitophagy receptors and upstream transcriptional regulators. CCA decreased mitophagy flux in both age groups, suggesting an improvement in organelle quality. CCA also reduced the exaggerated expression of TFEB evident in aged muscle, which may be promoting the age-induced increase in lysosomal markers. Thus, aged muscle possesses an elevated drive for autophagy and mitophagy which may contribute to the decline in organelle content observed with age, but which may serve to maintain mitochondrial quality. CCA improves organelle integrity and reduces mitophagy, illustrating that chronic exercise is a modality to improve muscle quality in aged populations.