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

TLDR

Muscle mass recovery after immobilisation is faster in young people than in older adults, but the cellular mechanisms driving this difference are unknown. This study examined the cellular and molecular regulation of muscle recovery in young and older adults following two weeks of immobilisation‑induced atrophy. Participants completed four weeks of supervised resistance training, during which myofibre area, Pax7‑positive satellite cells on type I and type II fibres, and expression of key growth and transcription factors were measured at baseline, after three days, and after four weeks of retraining. Older adults showed no gains in myofibre area or satellite cells after retraining, whereas younger adults exhibited increases, and the diminished regrowth in the elderly was associated with a smaller satellite cell response and age‑specific myostatin regulation, while other growth factor expressions were similar across ages.

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.