衰老
肌萎缩
生物
肌肉萎缩
内分泌学
萎缩
内科学
早衰
骨骼肌
平衡
线粒体
未折叠蛋白反应
炎症
细胞生物学
医学
免疫学
遗传学
内质网
作者
Caterina Tezze,Vanina Romanello,María Andrea Desbats,Gian Paolo Fadini,Mattia Albiero,Giulia Favaro,Stefano Ciciliot,María Eugenia Soriano,Valeria Morbidoni,Cristina Cerqua,Stefan Löefler,Helmut Kern,Claudio Franceschi,Stefano Salvioli,Maria Conte,Bert Blaauw,Sandra Zampieri,Leonardo Salviati,Luca Scorrano,Marco Sandri
出处
期刊:Cell Metabolism
[Elsevier]
日期:2017-05-25
卷期号:25 (6): 1374-1389.e6
被引量:435
标识
DOI:10.1016/j.cmet.2017.04.021
摘要
Mitochondrial dysfunction occurs during aging, but its impact on tissue senescence is unknown. Here, we find that sedentary but not active humans display an age-related decline in the mitochondrial protein, optic atrophy 1 (OPA1), that is associated with muscle loss. In adult mice, acute, muscle-specific deletion of Opa1 induces a precocious senescence phenotype and premature death. Conditional and inducible Opa1 deletion alters mitochondrial morphology and function but not DNA content. Mechanistically, the ablation of Opa1 leads to ER stress, which signals via the unfolded protein response (UPR) and FoxOs, inducing a catabolic program of muscle loss and systemic aging. Pharmacological inhibition of ER stress or muscle-specific deletion of FGF21 compensates for the loss of Opa1, restoring a normal metabolic state and preventing muscle atrophy and premature death. Thus, mitochondrial dysfunction in the muscle can trigger a cascade of signaling initiated at the ER that systemically affects general metabolism and aging.
科研通智能强力驱动
Strongly Powered by AbleSci AI