Veneto Institute of Molecular Medicine, Via Orus 2, 35129 Padova, Italy.
Department of Biomedical Sciences, University of Padova, Via G. Colombo 3, 35100 Padova, Italy.
Int J Mol Sci. 2020 Dec 23;22(1):91. doi: 10.3390/ijms22010091.
Sarcopenia is a chronic disease characterized by the progressive loss of skeletal muscle mass, force, and function during aging. It is an emerging public problem associated with poor quality of life, disability, frailty, and high mortality. A decline in mitochondria quality control pathways constitutes a major mechanism driving aging sarcopenia, causing abnormal organelle accumulation over a lifetime. The resulting mitochondrial dysfunction in sarcopenic muscles feedbacks systemically by releasing the myomitokines fibroblast growth factor 21 (FGF21) and growth and differentiation factor 15 (GDF15), influencing the whole-body homeostasis and dictating healthy or unhealthy aging. This review describes the principal pathways controlling mitochondrial quality, many of which are potential therapeutic targets against muscle aging, and the connection between mitochondrial dysfunction and the myomitokines FGF21 and GDF15 in the pathogenesis of aging sarcopenia.
肌肉减少症是一种慢性疾病，其特征是随着年龄的增长，骨骼肌质量、力量和功能逐渐丧失。它是一个与生活质量差、残疾、虚弱和高死亡率相关的新兴公共问题。线粒体质量控制途径的下降是导致衰老性肌肉减少症的主要机制之一，它导致一生中细胞器的异常积累。由此产生的肌肉减少症肌肉中的线粒体功能障碍通过释放肌细胞因子成纤维细胞生长因子 21（FGF21）和生长分化因子 15（GDF15）进行全身性反馈，影响全身的动态平衡，决定健康或不健康的衰老。本综述描述了控制线粒体质量的主要途径，其中许多途径是针对肌肉衰老的潜在治疗靶点，以及线粒体功能障碍与肌细胞因子 FGF21 和 GDF15 在衰老性肌肉减少症发病机制中的联系。
