高强度间歇训练可缓解肌肉疏松症并抑制肌细胞衰老调节因子 EEF1E1

IF 8.9 1区 医学 Journal of Cachexia, Sarcopenia and Muscle Pub Date : 2024-09-14 DOI:10.1002/jcsm.13600
Yaoshan Dun, Wenliang Zhang, Yang Du, Kangling Xie, Yuan Liu, Cui Li, Ling Qiu, Siqian Fu, Thomas P. Olson, Yuqiong Long, Baiyang You, Suixin Liu
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We explored the relationship between a HIIT‐specific protein relative to MICT, identified via comparative proteomic analysis, eukaryotic translation elongation factor 1 epsilon 1 (EEF1E1) and sarcopenia in a paired case–control study of elderly individuals (aged over 65). Young (3 months old) and aged (20 months old) mice were randomized to sedentary, HIIT and MICT groups (five sessions/week for 4 weeks; <jats:italic>n</jats:italic> = 8 for each group). Measurements included skeletal muscle index, hand grip strength, expression of atrophic markers Atrogin1 and MuRF1 and differentiation markers MyoD, myogenin and MyHC‐II via western blotting. We examined the impact of EEF1E1 siRNA and recombinant protein on D‐galactose‐induced myoblast senescence, measuring senescence‐associated β‐galactosidase and markers like p21 and p53.ResultsThe crossover trial, including 10 sedentary adults (32 years old, IQR 31–32) demonstrated significant alterations in the abundance of 21 plasma proteins after HIIT compared with MICT. In the paired case–control study of 84 older adults (84 years old, IQR 69–81; 52% female), EEF1E1 was significantly increased in those with sarcopenia compared to those without (14.68 [95%CI, 2.02–27.34] pg/mL, <jats:italic>p</jats:italic> = 0.03) and was associated with skeletal muscle index (<jats:italic>R</jats:italic><jats:sup>2</jats:sup> = 0.51, <jats:italic>p</jats:italic> &lt; 0.001) and hand grip strength (<jats:italic>R</jats:italic><jats:sup>2</jats:sup> = 0.54, <jats:italic>p</jats:italic> &lt; 0.001). 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引用次数: 0

摘要

背景缓解肌肉疏松症的最佳运动方案仍不确定。本研究旨在探讨高强度间歇训练(HIIT)与中等强度持续训练(MICT)相比,在改善肌肉疏松症方面的功效。方法 我们进行了一项随机交叉试验,以评估血浆蛋白质组对急性 HIIT(4 次 4 分钟高强度间歇,最大运动量为 70%,再交替进行 4 分钟,最大运动量为 30%)与 MICT(最大运动量保持在 50%)的反应。我们在一项针对老年人(65 岁以上)的配对病例对照研究中,探讨了通过比较蛋白质组分析确定的相对于 MICT 的 HIIT 特异性蛋白质、真核翻译伸长因子 1 epsilon 1 (EEF1E1) 与肌肉疏松症之间的关系。年轻(3 个月大)和年老(20 个月大)的小鼠被随机分为静坐组、HIIT 组和 MICT 组(每星期五次,共四周;每组 n = 8)。测量指标包括骨骼肌指数、手部握力、萎缩标志物 Atrogin1 和 MuRF1 的表达,以及通过 Western 印迹检测分化标志物 MyoD、myogenin 和 MyHC-II 的表达。我们检测了 EEF1E1 siRNA 和重组蛋白对 D-半乳糖诱导的成肌细胞衰老的影响,测量了衰老相关的 β-半乳糖苷酶以及 p21 和 p53 等标记物。结果这项交叉试验包括 10 名久坐的成年人(32 岁,IQR 31-32),结果表明与 MICT 相比,HIIT 后 21 种血浆蛋白的丰度发生了显著变化。在对 84 名老年人(84 岁,IQR 69-81;52% 为女性)进行的配对病例对照研究中,与无肌肉疏松症的老年人相比,有肌肉疏松症的老年人的 EEF1E1 显著增加(14.68 [95%CI, 2.02-27.34] pg/mL,p = 0.03),并与骨骼肌指数(R2 = 0.51,p <0.001)和手部握力(R2 = 0.54,p <0.001)相关。在临床前研究中,与年轻小鼠相比,老年小鼠骨骼肌中的 EEF1E1 mRNA 和蛋白质水平较高,同时肌肉质量和力量较低,细胞衰老和蛋白质降解标记物增加,肌肉分化效率降低(均为 p <0.05)。与 MICT 相比,HIIT 能更有效地减少 EEF1E1 的表达,缓解老年小鼠与年龄相关的肌肉衰退和萎缩。值得注意的是,通过 siRNA 下调 EEF1E1 能显著抵消 D-半乳糖诱导的成肌细胞衰老,这体现在肌肉蛋白降解标志物的减少和肌肉分化效率的提高(所有 p < 0.05)。相反,增加 EEF1E1 水平的处理会加速衰老过程(p < 0.05)。结论这项研究强调了 HIIT 作为预防和治疗肌肉疏松症的潜在方法的潜力,同时也强调了 EEF1E1 作为潜在干预目标的重要性。
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High‐Intensity Interval Training Mitigates Sarcopenia and Suppresses the Myoblast Senescence Regulator EEF1E1
BackgroundThe optimal exercise regimen for alleviating sarcopenia remains uncertain. This study aimed to investigate the efficacy of high‐intensity interval training (HIIT) over moderate‐intensity continuous training (MICT) in ameliorating sarcopenia.MethodsWe conducted a randomized crossover trial to evaluate plasma proteomic reactions to acute HIIT (four 4‐min high‐intensity intervals at 70% maximal capacity alternating with 4 min at 30%) versus MICT (constant 50% maximal capacity) in inactive adults. We explored the relationship between a HIIT‐specific protein relative to MICT, identified via comparative proteomic analysis, eukaryotic translation elongation factor 1 epsilon 1 (EEF1E1) and sarcopenia in a paired case–control study of elderly individuals (aged over 65). Young (3 months old) and aged (20 months old) mice were randomized to sedentary, HIIT and MICT groups (five sessions/week for 4 weeks; n = 8 for each group). Measurements included skeletal muscle index, hand grip strength, expression of atrophic markers Atrogin1 and MuRF1 and differentiation markers MyoD, myogenin and MyHC‐II via western blotting. We examined the impact of EEF1E1 siRNA and recombinant protein on D‐galactose‐induced myoblast senescence, measuring senescence‐associated β‐galactosidase and markers like p21 and p53.ResultsThe crossover trial, including 10 sedentary adults (32 years old, IQR 31–32) demonstrated significant alterations in the abundance of 21 plasma proteins after HIIT compared with MICT. In the paired case–control study of 84 older adults (84 years old, IQR 69–81; 52% female), EEF1E1 was significantly increased in those with sarcopenia compared to those without (14.68 [95%CI, 2.02–27.34] pg/mL, p = 0.03) and was associated with skeletal muscle index (R2 = 0.51, p < 0.001) and hand grip strength (R2 = 0.54, p < 0.001). In the preclinical study, aged mice exhibited higher EEF1E1 mRNA and protein levels in skeletal muscle compared to young mice, accompanied by a lower muscle mass and strength, increased cellular senescence and protein degradation markers and reduced muscle differentiation efficiency (all p < 0.05). HIIT reduced EEF1E1 expression and mitigated age‐related muscle decline and atrophy in aged mice more effectively than MICT. Notably, EEF1E1 downregulation via siRNA significantly counteracted D‐galactose‐induced myoblast senescence as evidenced by reduced markers of muscle protein degradation and improved muscle differentiation efficiency (all p < 0.05). Conversely, treatments that increased EEF1E1 levels accelerated the senescence process (p < 0.05). Further exploration indicated that the decrease in EEF1E1 was associated with increased SIRT1 level and enhanced autophagy.ConclusionsThis study highlights the potential of HIIT as a promising approach to prevent and treat sarcopenia while also highlighting EEF1E1 as a potential intervention target.
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来源期刊
Journal of Cachexia, Sarcopenia and Muscle
Journal of Cachexia, Sarcopenia and Muscle Medicine-Orthopedics and Sports Medicine
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期刊介绍: The Journal of Cachexia, Sarcopenia, and Muscle is a prestigious, peer-reviewed international publication committed to disseminating research and clinical insights pertaining to cachexia, sarcopenia, body composition, and the physiological and pathophysiological alterations occurring throughout the lifespan and in various illnesses across the spectrum of life sciences. This journal serves as a valuable resource for physicians, biochemists, biologists, dieticians, pharmacologists, and students alike.
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