Key Laboratory of Physical Fitness and Exercise Rehabilitation of Hunan Province, College of Physical Education, Hunan Normal University, 410012 Changsha, China.
Key Laboratory of Physical Fitness and Exercise Rehabilitation of Hunan Province, College of Physical Education, Hunan Normal University, 410012 Changsha, China.
Exp Gerontol. 2023 Sep;180:112265. doi: 10.1016/j.exger.2023.112265. Epub 2023 Jul 29.
Sarcopenia is a common skeletal muscle degenerative disease characterized by decreased skeletal muscle mass and mitochondrial dysfunction that involves microRNAs (miR) as regulatory factors in various pathways. Exercise reduces age-related oxidative damage and chronic inflammation and increases autophagy, among others. Moreover, whether aerobic exercise can regulate mitochondrial homeostasis by modulating the miR-128/insulin-like growth factor-1 (IGF-1) signaling pathway and can improve sarcopenia requires further investigation. Interestingly, zebrafish have been used as a model for aging research for over a decade due to their many outstanding advantages. Therefore, we established a model of zebrafish sarcopenia using d-galactose immersion and observed substantial changes, including reduced skeletal muscle cross-sectional area, increased tissue fibrosis, decreased motility, increased skeletal muscle reactive oxygen species, and notable alterations in mitochondrial morphology and function. We found that miR-128 expression was considerably upregulated, where as Igf1 and peroxisome proliferator-activated receptor gamma coactivator 1-alpha were significantly downregulated; moreover, mitochondrial homeostasis was reduced. Four weeks of aerobic exercise delayed sarcopenia progression and prevented the disruption of mitochondrial function and homeostasis. The genes related to atrophy and miR-128 were downregulated, Igf1 expression was considerably upregulated, and the phosphorylation levels of Pi3k, Akt, and Foxo3a were upregulated. Furthermore, mitochondrial respiration and homeostasis were enhanced. In conclusion, aerobic exercise improved skeletal muscle quality and function via the miR-128/IGF-1 signaling pathway, consequently ameliorating mitochondrial homeostasis in aging skeletal muscle.
肌肉减少症是一种常见的骨骼肌退行性疾病，其特征是骨骼肌质量减少和线粒体功能障碍，涉及 microRNAs（miR）作为各种途径的调节因子。运动可减少与年龄相关的氧化损伤和慢性炎症，增加自噬等。此外，有氧运动是否可以通过调节 miR-128/胰岛素样生长因子-1（IGF-1）信号通路来调节线粒体稳态，从而改善肌肉减少症，还需要进一步研究。有趣的是，由于其许多突出的优势，斑马鱼已被用作衰老研究的模型超过十年。因此，我们使用半乳糖浸泡建立了斑马鱼肌肉减少症模型，并观察到明显的变化，包括骨骼肌横截面积减少、组织纤维化增加、运动能力降低、骨骼肌活性氧增加以及线粒体形态和功能的显著改变。我们发现 miR-128 的表达显著上调，而 Igf1 和过氧化物酶体增殖物激活受体γ共激活因子 1-α显著下调；此外，线粒体稳态降低。四周的有氧运动延缓了肌肉减少症的进展，并防止了线粒体功能和稳态的破坏。与萎缩和 miR-128 相关的基因下调，Igf1 表达显著上调，Pi3k、Akt 和 Foxo3a 的磷酸化水平上调。此外，线粒体呼吸和稳态增强。总之，有氧运动通过 miR-128/IGF-1 信号通路改善骨骼肌质量和功能，从而改善衰老骨骼肌中的线粒体稳态。
