Irisin ameliorates age‐associated sarcopenia and metabolic dysfunction

作者：Mingwei Guo, Jing Yao, Jin Li, Jun Zhang, Dongmei Wang, Hui Zuo, Yi Zhang, Bo Xu, Yinzhao Zhong, Fei Shen, Jian Lü, Shuzhe Ding, Cheng Hu, Lingyan Xu, Junjie Xiao, Xinran Ma · 发表于：Journal of Cachexia Sarcopenia and Muscle · 年份：2022 · DOI：10.1002/jcsm.13141 · 被引用次数：156 · 研究领域：Adipose Tissue and Metabolism、Muscle Physiology and Disorders、Peroxisome Proliferator-Activated Receptors

BACKGROUND: Age-associated sarcopenia is characterized of progressed loss of skeletal muscle power, mass, and function, which affects human physical activity and life quality. Besides, accompanied with sarcopenia, aged population also faces a series of metabolic dysfunctions. Irisin, the cleaved form of fibronectin type III domain-containing protein 5 (FNDC5), is a myokine induced by exercise and has been shown to exert multiple beneficial effects on health. The goal of the study is to investigate the alterations of Fndc5/irisin in skeletal muscles during ageing and whether irisin administration could ameliorate age-associated sarcopenia and metabolic dysfunction. METHODS: The mRNA and protein levels of FNDC5/irisin in skeletal muscle and serum from 2- and 24-month-old mice or human subjects were analysed using qRT-PCR and western blot. FNDC5/irisin knockout mice were generated to investigate the consequences of FNDC5/irisin deletion on skeletal muscle mass, as well as morphological and molecular changes in muscle during ageing via histological and molecular analysis. To identify the therapeutic effects of chronic irisin treatment in mice during ageing, in vivo intraperitoneal administration of 2 mg/kg recombinant irisin was performed three times per week in ageing mice (14-month-old) for 4 months or in aged mice (22-month-old) for 1 month to systematically investigate irisin's effects on age-associated sarcopenia and metabolic performances, including grip strength, body weig...