Mingzheng Xie, You Weng
College of Physical Education and Sports Science, Hengyang Normal University, Hengyang, 421002, Hunan, China.
Department of Physical Education, Changsha Civil Affairs Vocational and Technical College, Changsha, 410004, Hunan, China.
Mol Cell Biochem. 2025 Aug 4. doi: 10.1007/s11010-025-05362-4.
Age-related reductions in skeletal muscle insulin responsiveness promote metabolic dysregulation and contribute to an elevated probability of type 2 diabetes onset. The malfunction of nutrient-responsive signaling routes, specifically AMP-activated protein kinase (AMPK) and mechanistic target of rapamycin (mTOR), constitutes a central component of this biological process. The integrated activity of these kinases in controlling energy dynamics, protein formation, and glucose processing is fundamental to ensure metabolic homeostasis in skeletal muscle tissue. Through its modulation of AMPK and mTOR pathways, exercise helps reinstate signaling equilibrium and supports better insulin efficacy in aging skeletal muscle. This review explores the molecular mechanisms by which different forms of exercise-endurance, resistance, and combined training-modulate the AMPK/mTOR axis in aging muscle. This analysis focuses on exercise-induced AMPK signaling as a catalyst for mitochondrial development, enhanced glucose processing, and intensified fatty acid breakdown, while also temporally coordinating mTOR activity to support muscle maintenance without exacerbating insulin resistance. By integrating insights from aging biology, exercise physiology, and molecular metabolism, this review highlights the therapeutic potential of targeting AMPK/mTOR signaling through physical activity to combat insulin resistance in the elderly.
与年龄相关的骨骼肌胰岛素反应性降低会促进代谢失调，并增加2型糖尿病发病的可能性。营养反应信号通路的功能障碍，特别是AMP激活的蛋白激酶（AMPK）和雷帕霉素靶蛋白（mTOR），是这一生物学过程的核心组成部分。这些激酶在控制能量动态、蛋白质合成和葡萄糖代谢方面的综合活性对于确保骨骼肌组织的代谢稳态至关重要。通过调节AMPK和mTOR通路，运动有助于恢复信号平衡，并支持衰老骨骼肌中更好的胰岛素效能。本综述探讨了不同形式的运动——耐力运动、抗阻运动和联合训练——调节衰老肌肉中AMPK/mTOR轴的分子机制。该分析聚焦于运动诱导的AMPK信号传导，它作为线粒体发育、增强葡萄糖代谢和强化脂肪酸分解的催化剂，同时还能适时协调mTOR活性，以支持肌肉维持而不加剧胰岛素抵抗。通过整合衰老生物学、运动生理学和分子代谢方面的见解，本综述强调了通过体育活动靶向AMPK/mTOR信号传导以对抗老年人胰岛素抵抗的治疗潜力。
