Marzetti Emanuele, Calvani Riccardo, Lorenzi Maria, Tanganelli Fabiana, Picca Anna, Bossola Maurizio, Menghi Amerigo, Bernabei Roberto, Landi Francesco
Department of Geriatrics, Neurosciences and Orthopedics, Catholic University of the Sacred Heart School of Medicine, Teaching Hospital "Agostino Gemelli", Rome, Italy.
Department of Geriatrics, Neurosciences and Orthopedics, Catholic University of the Sacred Heart School of Medicine, Teaching Hospital "Agostino Gemelli", Rome, Italy.
Exp Gerontol. 2016 Jul;80:1-5. doi: 10.1016/j.exger.2016.04.003. Epub 2016 Apr 7.
Sarcopenia has been proposed as a potentially amenable factor impacting the clinical outcomes of hip-fractured elderly. The identification of specific biological targets is therefore crucial to developing pharmacological interventions against age-related muscle wasting. The present work reports promising preliminary data on the association between alterations of myocyte quality control (MQC) signaling and sarcopenia in old patients with hip fracture.
Twenty-five elderly hip-fractured patients (20 women and 5 men; mean age 84.9±1.65years) were enrolled as part of the Sarcopenia in HIp FracTure (SHIFT) study. Intraoperative biopsies of the vastus lateralis muscle were obtained and assayed for the expression of a set of MQC signaling proteins. The presence of sarcopenia was established according to the European Working Group on Sarcopenia in Older People (EWGSOP) criteria, with bioelectrical impedance analysis used for fat-free mass estimation.
Sarcopenia was identified in 10 patients (40%). Protein expression of the mitochondrial fusion factor mitofusin (Mfn) 2 and the autophagy mediator microtubule-associated protein 1 light chain 3B (LC3B) was significantly lower in patients with sarcopenia compared with non-sarcopenic controls. No differences between groups were observed for Mfn1, optic atrophy protein 1 (OPA1), fission protein 1 (Fis1), and the master regulator of mitochondrial biogenesis peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α).
Data from this exploratory study show that a reduced expression of the mitochondrial fusion factor Mfn2 and the autophagy mediator LC3B is associated with sarcopenia in old hip-fractured patients. Future larger-scale studies are needed to corroborate these preliminary findings and determine whether MQC pathways may be targeted to improve muscle health and promote functional recovery in old patients with hip fracture.
肌肉减少症被认为是影响髋部骨折老年患者临床结局的一个潜在可调节因素。因此，确定特定的生物学靶点对于开发针对年龄相关肌肉萎缩的药物干预措施至关重要。本研究报告了老年髋部骨折患者中肌细胞质量控制（MQC）信号改变与肌肉减少症之间关联的有前景的初步数据。
25例老年髋部骨折患者（20例女性和5例男性；平均年龄84.9±1.65岁）作为髋部骨折肌肉减少症（SHIFT）研究的一部分被纳入。获取股外侧肌的术中活检样本，并检测一组MQC信号蛋白的表达。根据欧洲老年人肌肉减少症工作组（EWGSOP）标准确定肌肉减少症的存在，使用生物电阻抗分析来估计去脂体重。
10例患者（40%）被确定为肌肉减少症。与非肌肉减少症对照组相比，肌肉减少症患者中线粒体融合因子线粒体融合蛋白（Mfn）2和自噬调节因子微管相关蛋白1轻链3B（LC3B）的蛋白表达显著降低。在Mfn1、视神经萎缩蛋白1（OPA1）、裂变蛋白1（Fis1）以及线粒体生物发生的主要调节因子过氧化物酶体增殖物激活受体γ共激活因子1α（PGC-1α）方面，两组之间未观察到差异。
这项探索性研究的数据表明，线粒体融合因子Mfn2和自噬调节因子LC3B表达降低与老年髋部骨折患者的肌肉减少症相关。未来需要更大规模的研究来证实这些初步发现，并确定MQC通路是否可作为靶点来改善老年髋部骨折患者的肌肉健康并促进功能恢复。
