title: Mitochondrial morphology is altered in atrophied skeletal muscle of aged mice.
abstract: Skeletal muscle aging is associated with a progressive decline in muscle mass and strength, a process termed sarcopenia. Evidence suggests that accumulation of mitochondrial dysfunction plays a causal role in sarcopenia, which could be triggered by impaired mitophagy. Mitochondrial function, mitophagy and mitochondrial morphology are interconnected aspects of mitochondrial biology, and may coordinately be altered with aging. However, mitochondrial morphology has remained challenging to characterize in muscle, and whether sarcopenia is associated with abnormal mitochondrial morphology remains unknown. Therefore, we assessed the morphology of SubSarcolemmal (SS) and InterMyoFibrillar (IMF) mitochondria in skeletal muscle of young (8-12wk-old) and old (88-96wk-old) mice using a quantitative 2-dimensional transmission electron microscopy approach. We show that sarcopenia is associated with larger and less circular SS mitochondria. Likewise, aged IMF mitochondria were longer and more branched, suggesting increased fusion and/or decreased fission. Accordingly, although no difference in the content of proteins regulating mitochondrial dynamics (Mfn1, Mfn2, Opa1 and Drp1) was observed, a mitochondrial fusion index (Mfn2-to-Drp1 ratio) was significantly increased in aged muscles. Our results reveal that sarcopenia is associated with complex changes in mitochondrial morphology that could interfere with mitochondrial function and mitophagy, and thus contribute to aging-related accumulation of mitochondrial dysfunction and sarcopenia.
authors.affiliation: Département des Sciences de l'Activité Physique, Faculté des Sciences, UQAM, Montréal, Canada.|Groupe de Recherche en Activité Physique Adaptée, Montréal, Canada.|Centre de Recherche du CHU Sainte-Justine, Montréal, Canada.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Leduc-Gaudet
authors.affiliation: The Center for Mitochondrial and Epigenomic Medicine, Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Picard
authors.affiliation: Département des Sciences de l'Activité Physique, Faculté des Sciences, UQAM, Montréal, Canada.
authors.forename: Félix
authors.initials: F
authors.lastname: St-Jean Pelletier
authors.affiliation: Département des Sciences de l'Activité Physique, Faculté des Sciences, UQAM, Montréal, Canada.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Sgarioto
authors.affiliation: Département des Sciences de l'Activité Physique, Faculté des Sciences, UQAM, Montréal, Canada.
authors.forename: Marie-Joëlle
authors.initials: MJ
authors.lastname: Auger
authors.affiliation: Département de Neurosciences, Université de Montréal, Montréal, Canada.
authors.forename: Joanne
authors.initials: J
authors.lastname: Vallée
authors.affiliation: Département de Neurosciences, Université de Montréal, Montréal, Canada.|Groupe de Recherche sur le Système Nerveux Central, Montréal, Canada.
authors.forename: Richard
authors.initials: R
authors.lastname: Robitaille
authors.affiliation: Département des Sciences de l'Activité Physique, Faculté des Sciences, UQAM, Montréal, Canada.|Groupe de Recherche en Activité Physique Adaptée, Montréal, Canada.|Centre de Recherche du CHU Sainte-Justine, Montréal, Canada.
authors.forename: David H
authors.initials: DH
authors.lastname: St-Pierre
authors.affiliation: Département des Sciences de l'Activité Physique, Faculté des Sciences, UQAM, Montréal, Canada.|Groupe de Recherche en Activité Physique Adaptée, Montréal, Canada.|Centre de Recherche de l'Institut Universitaire de Gériatrie de Montréal, Montréal, Canada.
authors.forename: Gilles
authors.initials: G
authors.lastname: Gouspillou
mesh_terms: D000367:Age Factors; D000375:Aging / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D004195:Disease Models, Animal; D034281:Dynamins / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000378:metabolism; D008297:Male; D051379:Mice; D046529:Microscopy, Electron, Transmission; D008931:Mitochondria, Muscle / Q000378:metabolism / Q000648:ultrastructure*; D063154:Mitochondrial Dynamics; D053142:Mitochondrial Size; D018482:Muscle, Skeletal / Q000378:metabolism / Q000648:ultrastructure*; D053140:Organelle Shape; D055948:Sarcopenia / Q000378:metabolism / Q000473:pathology*
chemical_list: D020558:GTP Phosphohydrolases; C488750:Mfn1 protein, mouse; C488751:Mfn2 protein, mouse; C498809:Opa1 protein, mouse; C486391:Dnm1l protein, mouse; D034281:Dynamins
keywords: Gerotarget; atrophy; mitochondria; mitochondrial dynamics; muscle aging; sarcopenia