title: Association between myocyte quality control signaling and sarcopenia in old hip-fractured patients: Results from the Sarcopenia in HIp FracTure (SHIFT) exploratory study.
abstract: 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.
authors.affiliation: Department of Geriatrics, Neurosciences and Orthopedics, Catholic University of the Sacred Heart School of Medicine, Teaching Hospital "Agostino Gemelli", Rome, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Marzetti
authors.affiliation: Department of Geriatrics, Neurosciences and Orthopedics, Catholic University of the Sacred Heart School of Medicine, Teaching Hospital "Agostino Gemelli", Rome, Italy. Electronic address: riccardo.calvani@gmail.com.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Calvani
authors.affiliation: Department of Geriatrics, Neurosciences and Orthopedics, Catholic University of the Sacred Heart School of Medicine, Teaching Hospital "Agostino Gemelli", Rome, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Lorenzi
authors.affiliation: Department of Geriatrics, Neurosciences and Orthopedics, Catholic University of the Sacred Heart School of Medicine, Teaching Hospital "Agostino Gemelli", Rome, Italy.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Tanganelli
authors.affiliation: Department of Geriatrics, Neurosciences and Orthopedics, Catholic University of the Sacred Heart School of Medicine, Teaching Hospital "Agostino Gemelli", Rome, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Picca
authors.affiliation: Department of Surgery, Catholic University of the Sacred Heart School of Medicine, Teaching Hospital "Agostino Gemelli", Rome, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Bossola
authors.affiliation: Department of Geriatrics, Neurosciences and Orthopedics, Catholic University of the Sacred Heart School of Medicine, Teaching Hospital "Agostino Gemelli", Rome, Italy.
authors.forename: Amerigo
authors.initials: A
authors.lastname: Menghi
authors.affiliation: Department of Geriatrics, Neurosciences and Orthopedics, Catholic University of the Sacred Heart School of Medicine, Teaching Hospital "Agostino Gemelli", Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Bernabei
authors.affiliation: Department of Geriatrics, Neurosciences and Orthopedics, Catholic University of the Sacred Heart School of Medicine, Teaching Hospital "Agostino Gemelli", Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Landi
mesh_terms: D000369:Aged, 80 and over; D001284:Atrophy; D001343:Autophagy; D005260:Female; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D006620:Hip Fractures / Q000503:physiopathology*; D006801:Humans; D007558:Italy; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D063154:Mitochondrial Dynamics; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism*; D009132:Muscles / Q000503:physiopathology; D001678:Organelle Biogenesis; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000378:metabolism; D055948:Sarcopenia / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction
chemical_list: C476525:FIS1 protein, human; C502070:MAP1LC3B protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D020558:GTP Phosphohydrolases; C470018:MFN2 protein, human; C415198:OPA1 protein, human; C470017:Mfn1 protein, human
keywords: Fission; Fusion; Mitochondrial biogenesis; Muscle atrophy; Muscle biopsy; Orthogeriatrics