Development and characterisation of an in vitro human muscle self-repair model
Healthy skeletal muscle can regenerate after ischemic, mechanical, or toxin-induced injury, but age-related changes in skeletal muscle cells and their niche may impair their regeneration potential. While decline in myogenic capacity during ageing has been attributed mainly to dysfunctional satellite cells, a myofiber self-repair mechanism that does not require muscle progenitor cells is suggested as an alternative rapid and efficient response to localised injury as induced by physical exercise. To identify how skeletal muscle self-repair capacity in response to in vitro chemical injury differs in young and aged muscle cells, morphological, cell cycle and transcriptome analyses were performed on young and old muscle cells exposed to in vitro injury. We discovered reduced self-repair capacity of aged cells, as indicated by an attenuated recovery towards pre-injury muscle cell size and myogenic fusion index at the end of the regeneration period, compared with younger muscle cells that fully recovered. RNA-sequencing data showed significant enrichment of PI3K-Akt signalling in KEGG pathways and downregulation of GO processes associated with muscle development, differentiation and contraction in aged, but not in young muscle cells. Data presented here suggest the self-repair response to in vitro injury is impaired in aged vs. young muscle cells, providing further understanding of the cell-intrinsic capacity to repair muscle structure in healthy older people.