title: Ageing is associated with diminished muscle re-growth and myogenic precursor cell expansion early after immobility-induced atrophy in human skeletal muscle.
abstract: Recovery of skeletal muscle mass from immobilisation-induced atrophy is faster in young than older individuals, yet the cellular mechanisms remain unknown. We examined the cellular and molecular regulation of muscle recovery in young and older human subjects subsequent to 2 weeks of immobility-induced muscle atrophy. Retraining consisted of 4 weeks of supervised resistive exercise in 9 older (OM: mean age) 67.3, range 61-74 yrs) and 11 young (YM: mean age 24.4, range 21-30 yrs) males. Measures of myofibre area (MFA), Pax7-positive satellite cells (SCs) associated with type I and type II muscle fibres, as well as gene expression analysis of key growth and transcription factors associated with local skeletal muscle milieu, were performed after 2 weeks immobility (Imm) and following 3 days (+3d) and 4 weeks (+4wks) of retraining. OM demonstrated no detectable gains in MFA (vastus lateralis muscle) and no increases in number of Pax7-positive SCs following 4wks retraining, whereas YM increased their MFA (P < 0.05), number of Pax7-positive cells, and had more Pax7-positive cells per type II fibre than OM at +3d and +4wks (P < 0.05). No age-related differences were observed in mRNA expression of IGF-1Ea, MGF, MyoD1 and HGF with retraining, whereas myostatin expression levels were more down-regulated in YM compared to OM at +3d (P < 0.05). In conclusion, the diminished muscle re-growth after immobilisation in elderly humans was associated with a lesser response in satellite cell proliferation in combination with an age-specific regulation of myostatin. In contrast, expression of local growth factors did not seem to explain the age-related difference in muscle mass recovery.
authors.affiliation: Institute of Sports Medicine and Center of Healthy Ageing, Faculty of Health and Medical Sciences, University of Copenhagen, Bispebjerg Hospital, Denmark. csuetta@gmail.com
authors.forename: C
authors.initials: C
authors.lastname: Suetta
authors.forename: U
authors.initials: U
authors.lastname: Frandsen
authors.forename: A L
authors.initials: AL
authors.lastname: Mackey
authors.forename: L
authors.initials: L
authors.lastname: Jensen
authors.forename: L G
authors.initials: LG
authors.lastname: Hvid
authors.forename: M L
authors.initials: ML
authors.lastname: Bayer
authors.forename: S J
authors.initials: SJ
authors.lastname: Petersson
authors.forename: H D
authors.initials: HD
authors.lastname: Schrøder
authors.forename: J L
authors.initials: JL
authors.lastname: Andersen
authors.forename: P
authors.initials: P
authors.lastname: Aagaard
authors.forename: P
authors.initials: P
authors.lastname: Schjerling
authors.forename: M
authors.initials: M
authors.lastname: Kjaer
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics; D005260:Female; D017228:Hepatocyte Growth Factor / Q000235:genetics; D006801:Humans; D007103:Immobilization / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000502:physiology*; D009133:Muscular Atrophy / Q000503:physiopathology*; D017570:MyoD Protein / Q000235:genetics; D032446:Myoblasts / Q000502:physiology*; D055435:Myostatin / Q000235:genetics; D051763:PAX7 Transcription Factor / Q000235:genetics; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics; D050799:STAT5 Transcription Factor / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics; D055815:Young Adult
chemical_list: C493956:CDKN1A protein, human; C436291:CDKN1B protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C066855:HGF protein, human; C583557:IGF1 protein, human; C525911:MSTN protein, human; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D055435:Myostatin; D051763:PAX7 Transcription Factor; C497321:PAX7 protein, human; D012333:RNA, Messenger; D050799:STAT5 Transcription Factor; C494092:STAT5A protein, human; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D017228:Hepatocyte Growth Factor; D007334:Insulin-Like Growth Factor I; C496348:FGFR1 protein, human; D019859:Proto-Oncogene Proteins c-met; D051496:Receptor, Fibroblast Growth Factor, Type 1