title: Disuse atrophy and exercise rehabilitation in humans profoundly affects the expression of genes associated with the regulation of skeletal muscle mass.
abstract: Skeletal muscle atrophy occurs as a consequence of injury, illness, surgery, and muscle disuse, impacting appreciably on health care costs and patient quality of life, particularly in the absence of appropriate rehabilitation. The molecular mechanisms that regulate muscle mass during atrophy and rehabilitation in humans have not been elucidated, despite several robust candidate pathways being identified. Here, we induced skeletal muscle atrophy in healthy volunteers using two weeks of limb immobilization, and then stimulated the restoration of muscle mass with six weeks of supervised exercise rehabilitation. We determined muscle mass and function and performed targeted gene expression analysis at prescribed time points during immobilization and rehabilitation. For the first time, we have identified novel changes in gene expression following immobilization-induced atrophy and during a program of rehabilitative exercise that restored muscle mass and function. Furthermore, we have shown that exercise performed immediately following immobilization induces profound changes in the expression of a number of genes in favor of the restoration of muscle mass, within 24 h. This information will be of considerable importance to our understanding of how immobilization and contraction stimulate muscle atrophy and hypertrophy, respectively, and to the development of novel therapeutic strategies aimed at maintaining or restoring muscle mass.
authors.affiliation: Centre for Integrated Systems Biology and Medicine, School of Biomedical Sciences, The Medical School, University of Nottingham, Nottingham, NG7 2UH, UK. simonwynjones2003@yahoo.co.uk
authors.forename: Simon W
authors.initials: SW
authors.lastname: Jones
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Hill
authors.forename: Philip A
authors.initials: PA
authors.lastname: Krasney
authors.forename: Barbara
authors.initials: B
authors.lastname: O'Conner
authors.forename: Nicholas
authors.initials: N
authors.lastname: Peirce
authors.forename: Paul L
authors.initials: PL
authors.lastname: Greenhaff
mesh_terms: D000293:Adolescent; D000328:Adult; D002154:Calpain / Q000235:genetics; D003546:Cysteine Endopeptidases / Q000235:genetics; D015444:Exercise / Q000502:physiology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D051550:I-kappa B Kinase; D007103:Immobilization; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007537:Isometric Contraction; D008297:Male; D009097:Multienzyme Complexes / Q000235:genetics; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D009133:Muscular Atrophy / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology / Q000534:rehabilitation; D020966:Muscular Disorders, Atrophic / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology / Q000534:rehabilitation*; D055435:Myostatin; D009929:Organ Size; D046988:Proteasome Endopeptidase Complex; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000235:genetics; D025801:Ubiquitin / Q000235:genetics
chemical_list: C525911:MSTN protein, human; D009097:Multienzyme Complexes; D055435:Myostatin; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D025801:Ubiquitin; D007334:Insulin-Like Growth Factor I; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human; D002154:Calpain; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex