title: Physical exercise in aging human skeletal muscle increases mitochondrial calcium uniporter expression levels and affects mitochondria dynamics.
abstract: Age-related sarcopenia is characterized by a progressive loss of muscle mass with decline in specific force, having dramatic consequences on mobility and quality of life in seniors. The etiology of sarcopenia is multifactorial and underlying mechanisms are currently not fully elucidated. Physical exercise is known to have beneficial effects on muscle trophism and force production. Alterations of mitochondrial Ca2+homeostasis regulated by mitochondrial calcium uniporter (MCU) have been recently shown to affect muscle trophism in vivo in mice. To understand the relevance of MCU-dependent mitochondrial Ca2+uptake in aging and to investigate the effect of physical exercise on MCU expression and mitochondria dynamics, we analyzed skeletal muscle biopsies from 70-year-old subjects 9 weeks trained with either neuromuscular electrical stimulation (ES) or leg press. Here, we demonstrate that improved muscle function and structure induced by both trainings are linked to increased protein levels of MCU Ultrastructural analyses by electron microscopy showed remodeling of mitochondrial apparatus in ES-trained muscles that is consistent with an adaptation to physical exercise, a response likely mediated by an increased expression of mitochondrial fusion protein OPA1. Altogether these results indicate that the ES-dependent physiological effects on skeletal muscle size and force are associated with changes in mitochondrial-related proteins involved in Ca2+homeostasis and mitochondrial shape. These original findings in aging human skeletal muscle confirm the data obtained in mice and propose MCU and mitochondria-related proteins as potential pharmacological targets to counteract age-related muscle loss.
authors.affiliation: Ludwig Boltzmann Institute of Electrical Stimulation and Physical Rehabilitation, Vienna, Austria sanzamp@unipd.it.|Venetian Institute of Molecular Medicine, Padova, Italy.|Department of Biomedical Science, University of Padova, Padova, Italy.
authors.forename: Sandra
authors.initials: S
authors.lastname: Zampieri
authors.affiliation: Department of Biomedical Science, University of Padova, Padova, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Mammucari
authors.affiliation: Venetian Institute of Molecular Medicine, Padova, Italy.
authors.forename: Vanina
authors.initials: V
authors.lastname: Romanello
authors.affiliation: DAHFMO-Unit of Histology and Medical Embryology, IIM, Institute Pasteur Cenci-Bolognetti, Sapienza University of Rome, Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Barberi
authors.affiliation: Department of Neuroscience, Imaging and Clinical Sciences, CeSI-Met - Center for Research on Aging and Translational Medicine & DNICS University G. d'Annunzio, Chieti, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Pietrangelo
authors.affiliation: Department of Neuroscience, Imaging and Clinical Sciences, CeSI-Met - Center for Research on Aging and Translational Medicine & DNICS University G. d'Annunzio, Chieti, Italy.
authors.forename: Aurora
authors.initials: A
authors.lastname: Fusella
authors.affiliation: Department of Biomedical Science, University of Padova, Padova, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Mosole
authors.affiliation: Department of Biomedical Science, University of Padova, Padova, Italy.
authors.forename: Gaia
authors.initials: G
authors.lastname: Gherardi
authors.affiliation: Ludwig Boltzmann Institute of Electrical Stimulation and Physical Rehabilitation, Vienna, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Höfer
authors.affiliation: Ludwig Boltzmann Institute of Electrical Stimulation and Physical Rehabilitation, Vienna, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Löfler
authors.affiliation: Science and Research Centre, Institute for Kinesiology Research, University of Primorska, Koper, Slovenia.
authors.forename: Nejc
authors.initials: N
authors.lastname: Sarabon
authors.affiliation: Faculty of Physical Education and Sport, Comenius University, Bratislava, Slovakia.
authors.forename: Jan
authors.initials: J
authors.lastname: Cvecka
authors.affiliation: Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria.
authors.forename: Matthias
authors.initials: M
authors.lastname: Krenn
authors.affiliation: Institute of Electrodynamics, Microwave and Circuit Engineering, Vienna University of Technology, Vienna, Austria.|IRCCS Fondazione Ospedale San Camillo, Venezia, Italy.
authors.forename: Ugo
authors.initials: U
authors.lastname: Carraro
authors.affiliation: Ludwig Boltzmann Institute of Electrical Stimulation and Physical Rehabilitation, Vienna, Austria.
authors.forename: Helmut
authors.initials: H
authors.lastname: Kern
authors.affiliation: Department of Neuroscience, Imaging and Clinical Sciences, CeSI-Met - Center for Research on Aging and Translational Medicine & DNICS University G. d'Annunzio, Chieti, Italy.
authors.forename: Feliciano
authors.initials: F
authors.lastname: Protasi
authors.affiliation: DAHFMO-Unit of Histology and Medical Embryology, IIM, Institute Pasteur Cenci-Bolognetti, Sapienza University of Rome, Rome, Italy.|Center for Life Nano Science at Sapienza, Istituto Italiano di Tecnologia, Rome, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Musarò
authors.affiliation: Venetian Institute of Molecular Medicine, Padova, Italy.|Department of Biomedical Science, University of Padova, Padova, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Sandri
authors.affiliation: Venetian Institute of Molecular Medicine, Padova, Italy.
authors.forename: Rosario
authors.initials: R
authors.lastname: Rizzuto
mesh_terms: D000368:Aged; D000375:Aging; D001284:Atrophy; D015220:Calcium Channels / Q000378:metabolism*; D004558:Electric Stimulation; D015444:Exercise; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007537:Isometric Contraction; D008297:Male; D008928:Mitochondria / Q000502:physiology* / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000502:physiology* / Q000648:ultrastructure; D055948:Sarcopenia / Q000378:metabolism* / Q000517:prevention & control; D057185:Sedentary Behavior
chemical_list: D015220:Calcium Channels; C583557:IGF1 protein, human; C034703:mitochondrial calcium uniporter; D007334:Insulin-Like Growth Factor I
keywords: Aging skeletal muscle; electrical stimulation; mitochondria Ca2+ uptake