Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, L.go A. Gemelli 8, 00168 Rome, Italy.
Department of Geriatrics, Orthopedics and Rheumatology, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00618 Rome, Italy.
Int J Mol Sci. 2024 Feb 8;25(4):2052. doi: 10.3390/ijms25042052.
Sarcopenia, the age-associated decline in skeletal muscle mass and strength, is a condition with a complex pathophysiology. Among the factors underlying the development of sarcopenia are the progressive demise of motor neurons, the transition from fast to slow myosin isoform (type II to type I fiber switch), and the decrease in satellite cell number and function. Mitochondrial dysfunction has been indicated as a key contributor to skeletal myocyte decline and loss of physical performance with aging. Several systems have been implicated in the regulation of muscle plasticity and trophism such as the fine-tuned and complex regulation between the stimulator of protein synthesis, mechanistic target of rapamycin (mTOR), and the inhibitor of mTOR, AMP-activated protein kinase (AMPK), that promotes muscle catabolism. Here, we provide an overview of the molecular mechanisms linking mitochondrial signaling and quality with muscle homeostasis and performance and discuss the main pathways elicited by their imbalance during age-related muscle wasting. We also discuss lifestyle interventions (i.e., physical exercise and nutrition) that may be exploited to preserve mitochondrial function in the aged muscle. Finally, we illustrate the emerging possibility of rescuing muscle tissue homeostasis through mitochondrial transplantation.
肌肉减少症是一种与年龄相关的骨骼肌质量和力量下降的病症,其发病机制非常复杂。导致肌肉减少症发生的因素包括运动神经元的进行性丧失、肌球蛋白同工型(从快肌向慢肌肌球蛋白同工型转变)的转变,以及卫星细胞数量和功能的减少。线粒体功能障碍已被认为是导致骨骼肌细胞衰退和与衰老相关的身体机能下降的关键因素。有几个系统被牵涉到肌肉可塑性和营养的调节中,例如促进肌肉分解代谢的蛋白质合成刺激物、雷帕霉素靶蛋白(mTOR)和 mTOR 抑制剂、AMP 激活的蛋白激酶(AMPK)之间的精细和复杂的调节。在这里,我们概述了将线粒体信号与质量与肌肉动态平衡和性能联系起来的分子机制,并讨论了它们在与年龄相关的肌肉减少症过程中失衡所引发的主要途径。我们还讨论了可能被利用来维持老年肌肉中线粒体功能的生活方式干预(即体育锻炼和营养)。最后,我们说明了通过线粒体移植来恢复肌肉组织动态平衡的新可能性。