Mechanical and chemical activation of muscle satellite cells is perturbed in normal aged mice

Abstract

Age‐related muscle atrophy and the importance of satellite cells in muscle maintenance, growth and repair led us to examine the effects of mechanical stretch, nitric oxide (NO), and age on satellite cell (SC) activation and gene expression in normal young and old mice. Baseline variables (body mass, muscle mass, fiber cross‐sectional area (CSA), muscle strength, SC population, stretch activation and gene expression) were obtained from normal C57/BL6 mice at 3, 6, 8, 12 and 18 months‐of‐age. Activation was assayed by 3H‐thymidine incorporation into extensor digitorum longus (EDL) muscles isolated for culture with (S) or without stretching (US). In a second experiment, muscle from 8‐ and 18‐month old mice was treated with one or more of: stretch, L‐Arginine (LA); NO‐donors (isosorbide dinitrate (ISDN) and MyoNovin (MN) a new formulation); Nω‐nitro‐L‐Arginine methyl ester (LN). EDL muscles from 6‐month‐old mice required a greater stretch stimulus (20% vs. 10% length increase) than EDL from younger mice to increase SC activation. Stretch did not increase SC activation in mice older than 6 months‐of‐age. NO from either endogenous (LA) or exogenous (ISDN, MN) NO donors increased SC activation by stretch in 8‐ but not 18‐mo‐old EDLs. Perturbed sensitivity to mechanical stimulation and NO in 18‐mo‐old mice may partly explain loss of muscle mass, fiber CSA, relative grip strength and SC pool size with age. Similar to dystrophic muscle, a disrupted dystrophin‐glycoprotein complex and subsequent alteration in NO availability may affect the ability of native satellite cells to maintain or effectively regenerate aged muscle.Grant Funding SourceCanadian Space Agency Life Sciences