Neuromuscular electrical stimulation improves skeletal muscle regeneration through satellite cell fusion with myofibers in healthy elderly subjects

The aim was to determine whether neuromuscular electrical stimulation (NMES) affects skeletal muscle regeneration through a reduction of oxidative status in satellite cells of healthy elderly subjects. Satellite cells from the Vastus lateralis skeletal muscle of 12 healthy elderly subjects before and after 8 weeks of NMES were allowed to proliferate to provide myogenic populations of adult stem cells (myogenic precursor cells; MPCs). These MPCs were then investigated in terms of their proliferation, their basal cytoplasmic free Ca(2+) concentrations, and their expression of myogenic regulatory factors (PAX3, PAX7, MYF5, MYOD, MYOG) and microRNAs (miR-1, miR-133a/b, miR-206). The oxidative status of these MPCs was evaluated through superoxide anion production and superoxide dismutase and glutathione peroxidase activities. On dissected single skeletal myofibers, the nuclei were counted to determine the myonuclear density, the fiber phenotype, cross sectional area and tension developed. The MPCs obtained after NMES showed increased proliferation rates along with increased cytoplasmic free Ca(2+) concentrations and gene expression of MYOD and MYOG on MPCs. The muscle-specific miR-1, miR133a/b, miR-206 were up-regulated. This NMES significantly reduced superoxide anion production, along with a trend to reduction of superoxide dismutase activity. The NMES-dependent stimulation of muscle regeneration enhanced satellite cells fusion with mature skeletal fibers. NMES improved the regenerative capacity of skeletal muscle in elderly subjects. Accordingly, the skeletal muscle strength and mobility of NMES-stimulated elderly significantly improved. NMES may thus be further considered for clinical or ageing populations.