Yeo Dongwook
Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA.
Adv Exp Med Biol. 2025;1478:157-183. doi: 10.1007/978-3-031-88361-3_8.
Muscle disuse atrophy is characterized by a significant reduction in skeletal muscle mass and strength, primarily induced by prolonged periods of inactivity and inadequate mechanical stimulus. This condition is frequently encountered in clinical scenarios, especially in cases where patients undergo limb immobilization due to injuries or suffer from spinal cord impairments. The severity of muscle atrophy is often exacerbated by additional factors, such as advancing age and nutritional deficiencies, underscoring the multifaceted nature of this condition. Over the last two decades, significant advancements have been made in understanding the processes that lead to muscle degradation. Insights into the molecular and cellular mechanisms driving muscle catabolism in the absence of regular physical activity have been gained through research utilizing rodent models such as hindlimb unloading and immobilization, denervation, and spinal cord isolation. These experimental models have provided information on the morphological and functional deterioration as well as the extent of understanding of the molecular and cellular processes in response to disuse-induced muscle wasting. Despite these efforts, the therapeutic options for ameliorating muscle disuse atrophy are limited. Resistance training has been identified as the most effective intervention for reversing muscle mass and strength loss, yet it may only be feasible for some patients due to physical limitations or a lack of motivation to engage in intensive exercise routines. In response to these challenges, ongoing research is focused on identifying alternative therapeutic strategies, encompassing both pharmacological and non-pharmacological approaches, aimed at either preventing the onset of muscle atrophy or facilitating recovery following atrophic events. The implications of muscle disuse atrophy extend beyond clinical manifestations, impacting individuals' quality of life by impairing physical endurance and the capacity to perform daily activities. This chapter aims to offer an exhaustive summary of the various signals, pathways, and breakdown mechanisms implicated in muscle atrophy. Additionally, it will present the latest developments in therapeutic strategies addressing this condition.
肌肉废用性萎缩的特征是骨骼肌质量和力量显著下降,主要由长期不活动和机械刺激不足引起。这种情况在临床中经常出现,尤其是在患者因受伤而肢体固定或患有脊髓损伤的情况下。肌肉萎缩的严重程度往往会因年龄增长和营养缺乏等其他因素而加剧,这突出了这种情况的多面性。在过去二十年中,在理解导致肌肉退化的过程方面取得了重大进展。通过利用诸如后肢卸载和固定、去神经支配以及脊髓隔离等啮齿动物模型的研究,已经深入了解了在缺乏定期体育活动的情况下驱动肌肉分解代谢的分子和细胞机制。这些实验模型提供了关于形态和功能恶化以及对废用性肌肉萎缩所引发的分子和细胞过程的理解程度的信息。尽管做出了这些努力,但改善肌肉废用性萎缩的治疗选择仍然有限。阻力训练已被确定为逆转肌肉质量和力量损失的最有效干预措施,但由于身体限制或缺乏参与高强度锻炼的动力,它可能仅对某些患者可行。为应对这些挑战,正在进行的研究集中在确定替代治疗策略,包括药理学和非药理学方法,旨在预防肌肉萎缩的发生或促进萎缩事件后的恢复。肌肉废用性萎缩的影响不仅限于临床表现,还会通过损害身体耐力和进行日常活动的能力来影响个人的生活质量。本章旨在详尽总结与肌肉萎缩相关的各种信号、途径和分解机制。此外,还将介绍针对这种情况的治疗策略的最新进展。