Age influences the early events of skeletal muscle regeneration: Studies of whole muscle grafts transplanted between young (8 weeks) and old (13–21 months) mice

Abstract

Injured skeletal muscle generally regenerates less efficiently with age, but little is understood about the effects of ageing on the very early inflammatory and neovascular events in the muscle repair process. This study used a total of 174 whole muscle grafts transplanted within and between young and old mice to analyse the effects of ageing on the early inflammatory response in two strains of mice (BALB/c and SJL/J). There was a very slight delay in the early inflammatory response, and in the appearance of myotubes at day 4 in BALB/c muscle grafted into an old host environment (implicating systemic events). In SJL/J mice, the initial speed of the inflammatory response was slightly delayed with old muscle grafts regardless of host age (implicating muscle-derived factors), while an old host environment transiently affected myogenesis (myotube formation). The slight delays in inflammatory and neovascular responses in old mice did not dramatically impact on the overall formation of new muscle. The neovascular response to injured young and old muscle tissue was further analysed using the corneal micropocket assay. This showed a very clear 1–2 day delay in angiogenesis induced by old versus young BALB/c muscle tissue implanted into the young rat cornea, indicating that new blood vessel formation is at least partly determined by muscle-derived factors. Taken together these results indicate that, while there are slight age-associated delays in inflammation and neovascularisation in response to injured muscle, there is no detrimental effect on myogenesis in the mouse model used in this study.