Xu Xin, Wen Zixing
Department of Rehabilitation Therapy, School of Health, Shanghai Normal University Tianhua College Shanghai, China.
Department of Rehabilitation, School of International Medical Technology, Shanghai Sanda University Shanghai, China.
Am J Clin Exp Immunol. 2023 Dec 15;12(6):109-126. eCollection 2023.
Sarcopenia, characterized by the insidious reduction of skeletal muscle mass and strength, detrimentally affects the quality of life in elderly cohorts. Present therapeutic strategies are confined to physiotherapeutic interventions, signaling a critical need for elucidation of the etiological underpinnings to facilitate the development of innovative pharmacotherapies. Recent scientific inquiries have associated mitochondrial dysfunction and inflammation with the etiology of sarcopenia. Mitochondria are integral to numerous fundamental cellular processes within muscle tissue, including but not limited to apoptosis, autophagy, signaling via reactive oxygen species, and the maintenance of protein equilibrium. Deviations in mitochondrial dynamics, coupled with compromised oxidative capabilities, autophagic processes, and protein equilibrium, result in disturbances to muscular architecture and functionality. Mitochondrial dysfunction is particularly detrimental as it diminishes oxidative phosphorylation, escalates apoptotic activity, and hinders calcium homeostasis within muscle cells. Additionally, deleterious feedback loops of deteriorated respiration, exacerbated oxidative injury, and diminished quality control mechanisms precipitate the acceleration of muscular senescence. Notably, mitochondria exhibiting deficient energetic metabolism are pivotal in precipitating the shift from normative muscle aging to a pathogenic state. This analytical review meticulously examines the complex interplay between mitochondrial dysfunction, persistent inflammation, and the pathogenesis of sarcopenia. It underscores the imperative to alleviate inflammation and amend mitochondrial anomalies within geriatric populations as a strategy to forestall and manage sarcopenia. An initial overview provides a succinct exposition of sarcopenia and its clinical repercussions. The discourse then progresses to an examination of the direct correlation between mitochondrial dysfunction and the genesis of sarcopenia. Concomitantly, it accentuates potential synergistic effects between inflammatory responses and mitochondrial insufficiencies during the aging of skeletal muscle, thereby casting light upon emergent therapeutic objectives. In culmination, this review distills the prevailing comprehension of the mitochondrial and inflammatory pathways implicated in sarcopenia and delineates extant lacunae in knowledge to orient subsequent scientific inquiry.
肌肉减少症的特征是骨骼肌质量和力量逐渐隐匿性下降,对老年人群的生活质量产生不利影响。目前的治疗策略仅限于物理治疗干预,这表明迫切需要阐明其病因基础,以促进创新药物疗法的开发。最近的科学研究将线粒体功能障碍和炎症与肌肉减少症的病因联系起来。线粒体对于肌肉组织内众多基本细胞过程不可或缺,包括但不限于细胞凋亡、自噬、活性氧信号传导以及蛋白质平衡的维持。线粒体动力学的偏差,再加上氧化能力、自噬过程和蛋白质平衡受损,会导致肌肉结构和功能紊乱。线粒体功能障碍尤其有害,因为它会减少氧化磷酸化、加剧细胞凋亡活性并阻碍肌肉细胞内的钙稳态。此外,呼吸功能恶化、氧化损伤加剧和质量控制机制减弱的有害反馈回路会加速肌肉衰老。值得注意的是,表现出能量代谢不足的线粒体在促使从正常肌肉衰老向致病状态转变中起关键作用。这篇分析性综述详细研究了线粒体功能障碍、持续性炎症与肌肉减少症发病机制之间的复杂相互作用。它强调了在老年人群中减轻炎症和纠正线粒体异常作为预防和管理肌肉减少症策略的紧迫性。初步概述简要阐述了肌肉减少症及其临床影响。接着论述转向研究线粒体功能障碍与肌肉减少症发生之间的直接关联。同时,它强调了在骨骼肌衰老过程中炎症反应和线粒体功能不足之间潜在的协同作用,从而揭示新出现的治疗目标。最后,本综述总结了对涉及肌肉减少症的线粒体和炎症途径的现有理解,并勾勒出知识上现存的空白,为后续科学探究指明方向。