Department of Medicine and Surgery, LUM University, Casamassima, 70100 Bari, Italy; Fondazione Policlinico Universitario "Agostino Gemelli" IRCSS, 00168 Rome, Italy.
Department of Medicine and Surgery, LUM University, Casamassima, 70100 Bari, Italy; DAHFMO Unit of Histology and Medical Embryology, Sapienza University of Rome, 00161 Rome, Italy.
Exp Gerontol. 2023 Jul;178:112204. doi: 10.1016/j.exger.2023.112204. Epub 2023 May 18.
The maintenance of functional health is pivotal for achieving independent life in older age. The aged muscle is characterized by ultrastructural changes, including loss of type I and type II myofibers and a greater proportion of cytochrome c oxidase deficient and succinate dehydrogenase positive fibers. Both intrinsic (e.g., altered proteostasis, DNA damage, and mitochondrial dysfunction) and extrinsic factors (e.g., denervation, altered metabolic regulation, declines in satellite cells, and inflammation) contribute to muscle aging. Being a hub for several cellular activities, mitochondria are key to myocyte viability and mitochondrial dysfunction has been implicated in age-associated physical decline. The maintenance of functional organelles via mitochondrial quality control (MQC) processes is, therefore, crucial to skeletal myofiber viability and organismal health. The autophagy-lysosome pathway has emerged as a critical step of MQC in muscle by disposing organelles and proteins via their tagging for autophagosome incorporation and delivery to the lysosome for clearance. This pathway was found to be altered in muscle of physically inactive older adults. A relationship between this pathway and muscle tissue composition of the lower extremities as well as physical performance was also identified. Therefore, integrating muscle structure and myocyte quality control measures in the evaluation of muscle health may be a promising strategy for devising interventions fostering muscle health.
维持功能健康对于老年人实现独立生活至关重要。老年肌肉的特点是超微结构发生变化，包括 I 型和 II 型肌纤维的丧失，以及更多比例的细胞色素 c 氧化酶缺乏和琥珀酸脱氢酶阳性纤维。内在因素（例如，蛋白质稳态改变、DNA 损伤和线粒体功能障碍）和外在因素（例如，去神经支配、代谢调节改变、卫星细胞减少和炎症）都导致肌肉衰老。线粒体作为几种细胞活动的中心，是肌细胞活力的关键，线粒体功能障碍与年龄相关的身体衰退有关。通过线粒体质量控制 (MQC) 过程维持功能细胞器对于骨骼肌纤维活力和机体健康至关重要。自噬-溶酶体途径已成为肌肉中 MQC 的关键步骤，通过将细胞器和蛋白质标记为自噬体的一部分，将其递送至溶酶体进行清除。在体力活动较少的老年成年人的肌肉中发现了这种途径的改变。还发现该途径与下肢肌肉组织成分和身体表现之间存在关系。因此，在评估肌肉健康时将肌肉结构和肌细胞质量控制措施结合起来可能是制定促进肌肉健康干预措施的有前途的策略。
