Wang Yilin, Meng Jingyuan, Zhang Jiechao, Tian Lichao, Wei Wenrui, Tang Xiaoye, Zhang Qian, Ding Daofang, Wang Xuepeng, Guo Zicheng, He Yong
Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Ann Med. 2025 Dec;57(1):2540598. doi: 10.1080/07853890.2025.2540598. Epub 2025 Aug 1.
Muscle atrophy-the decline of skeletal muscle volume and function-is pervasive in chronic disease, aging, and inactivity. As the primary driver of human mobility and metabolic health, skeletal muscle loss diminishes quality of life and increases healthcare burden. Atrophy impairs recovery and prognosis by reducing metabolic capacity, accelerating systemic protein catabolism, and compromising the biomechanical support necessary for movement and respiration. Although core molecular pathways and cellular changes are well characterized, the role of mechanical cues in modulating these mechanisms remains underexplored.
Our review reveals five convergent atrophy drivers-mechanical unloading, ECM alterations, mitochondrial dysfunction/oxidative stress, inflammation, and endocrine imbalance-that converge on inhibited mTORC1 signaling, activated FoxO/UPS/autophagy, and impaired satellite-cell function. Quantitative data show that axial stretch preserves PI3K/Akt/mTOR activity, with phosphorylated Akt levels increasing by two- to three-fold and fiber cross-sectional area expanding by 10%-20%; low-intensity compression activates AMPK and autophagy, with AMPK phosphorylation rising by 1.5-fold without triggering excessive protein breakdown; and shear stress enhances VEGF and Nrf2-mediated angiogenesis and antioxidant defenses, doubling VEGF expression and reducing ROS levels by 25% to mitigate neurogenic atrophy. Moreover, stem-cell myogenic differentiation is optimized on 3D biomimetic substrates with stiffness from 11 to 17 kPa under physiological loading, and advances in biomaterials and tissue engineering enable more accurate muscle-tissue models.
Translating these biomechanical insights into tailored clinical interventions-combining stretch, compression, and shear modalities with biomaterials, stem-cell technologies, and personalized exercise programs- holds promise for preventing and reversing muscle atrophy across diverse patient populations.
肌肉萎缩——骨骼肌体积和功能的衰退——在慢性疾病、衰老和缺乏运动的情况下普遍存在。作为人类活动能力和代谢健康的主要驱动因素，骨骼肌流失会降低生活质量并增加医疗负担。萎缩通过降低代谢能力、加速全身蛋白质分解代谢以及损害运动和呼吸所需的生物力学支持，从而损害恢复能力和预后。尽管核心分子途径和细胞变化已得到充分表征，但机械信号在调节这些机制中的作用仍未得到充分探索。
我们的综述揭示了五个共同的萎缩驱动因素——机械卸载、细胞外基质改变、线粒体功能障碍/氧化应激、炎症和内分泌失衡——这些因素共同作用于抑制的mTORC1信号传导、激活的FoxO/泛素蛋白酶体系统/自噬以及受损的卫星细胞功能。定量数据表明，轴向拉伸可保持PI3K/Akt/mTOR活性，磷酸化Akt水平增加两到三倍，纤维横截面积扩大10%-20%；低强度压缩激活AMPK和自噬，AMPK磷酸化增加1.5倍，而不会引发过度的蛋白质分解；剪切应力增强VEGF和Nrf2介导的血管生成和抗氧化防御，使VEGF表达增加一倍，并使ROS水平降低25%，以减轻神经源性萎缩。此外，在生理负荷下，干细胞的肌源性分化在刚度为11至17kPa的3D仿生基质上得到优化，生物材料和组织工程的进展使更精确的肌肉组织模型成为可能。
将这些生物力学见解转化为量身定制的临床干预措施——将拉伸、压缩和剪切方式与生物材料、干细胞技术和个性化运动计划相结合——有望预防和逆转不同患者群体的肌肉萎缩。
