Ageing is associated with diminished muscle re-growth and myogenic precursor cell expansion early after immobility-induced atrophy in human skeletal muscle - PubMed (original) (raw)

Randomized Controlled Trial

. 2013 Aug 1;591(15):3789-804.

doi: 10.1113/jphysiol.2013.257121. Epub 2013 Jun 3.

U Frandsen, A L Mackey, L Jensen, L G Hvid, M L Bayer, S J Petersson, H D Schrøder, J L Andersen, P Aagaard, P Schjerling, M Kjaer

Affiliations

Randomized Controlled Trial

Ageing is associated with diminished muscle re-growth and myogenic precursor cell expansion early after immobility-induced atrophy in human skeletal muscle

C Suetta et al. J Physiol. 2013.

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.

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Figures

Figure 1

Figure 1. Changes in myofibre cross-sectional area following 2 weeks of immobilisation and 4 weeks of retraining in young and older human individuals

A, type I myofibre cross-sectional area. B, type II myofibre cross-sectional area. Open bars represent young (_n_= 9) and grey bars represent older individuals (_n_= 7). Pre, ∼1 week prior to the immobilisation; Imm, after 2 weeks of immobilisation; +4wks, after 28 days of retraining. *Time effect, P < 0.05, compared to Pre. #Time effect, P < 0.05 compared to Imm. ∞Age effect, P < 0.05 young compared to old within time point. Group mean data ± SEM.

Figure 2

Figure 2. Pax7-positive cells associated with type I and II myofibres

Immunohistochemically detected Pax7+ cells, type I myosin and laminin on a muscle biopsy cross-section. Pax7+ cells (black arrows) are visualised by light microscopy (brown; upper left, ‘Pax7’), and type I myosin staining (red) used to indicate Pax7+ cells associated with type I fibres (A4.951+; red) or type II fibres (unstained; upper right, ‘A4.951’). Laminin staining (green) was used to mark the myofibre basal membrane (lower left, ‘Laminin’). In the merged image of the three stainings for Pax7, type I myosin (A4.951) and laminin, a Pax7+ cell was located within a type I fibre while two Pax7+ cells were identified in type II fibres (lower right, ‘Merged’). Scale bar, 100 μm.

Figure 3

Figure 3. Pax7-positive cells pre- and post immobilisation and following 4 weeks of retraining: association with fibre type

A, number of Pax7+ cells associated with fibre type I. B, number of Pax7-positive satellite cells associated with fibre type II. +3d, after 3 days of retraining. *Time effect, P < 0.05 compared to Pre. ∞Age effect, P < 0.05 difference between young and old within time point. Data are means ± SEM.

Figure 4

Figure 4. mRNA values relative to the young group at baseline (Pre)

*Age effect, P < 0.05 young compared to old. Data are geometric means ± back-transformed SEM.

Figure 5

Figure 5. mRNA expression levels relative to baseline following 2 weeks of immobilisation and 4 weeks of retraining

A, IGF-1Ea; B, MGF; C, MyoD1; D, myogenin; E, HGF; F, c-Met; G, FGF2; H, FGFR1; I, Pax7; J, myostatin; K, CDKN1A (p21); L, CDKN1B (p27). *Time effect, P < 0.05 compared to Pre. #Time effect, P < 0.05 compared to Imm. §Time effect, P < 0.05 compared to +3d. ∞Age effect, P < 0.05 young compared to old. Data are geometric means ± back-transformed SEM.

Figure 5

Figure 5. mRNA expression levels relative to baseline following 2 weeks of immobilisation and 4 weeks of retraining

A, IGF-1Ea; B, MGF; C, MyoD1; D, myogenin; E, HGF; F, c-Met; G, FGF2; H, FGFR1; I, Pax7; J, myostatin; K, CDKN1A (p21); L, CDKN1B (p27). *Time effect, P < 0.05 compared to Pre. #Time effect, P < 0.05 compared to Imm. §Time effect, P < 0.05 compared to +3d. ∞Age effect, P < 0.05 young compared to old. Data are geometric means ± back-transformed SEM.

Figure 6

Figure 6. Association between changes in myofibre area and number of Pax7+ cells

A, number of Pax7+ cells versus fibre area for all fibres collapsed or separated into type I or II fibres post immobilisation (Imm). B, relative changes in myofibre area (MFA, type I or type II) following 4 weeks of retraining (relative to post immobilisation) versus the change in number of Pax7+ cells (total, type I associated and type II associated). Open triangles, young individuals; filled triangles, older individuals.

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