Age-related failure of muscle regeneration in the dystrophic dy2J/dy2J mouse.

The progressive wasting of muscle tissue in muscular dystrophies is apparently due to an inability of muscle regeneration to keep pace with the continued degeneration of fibers. However, these is no direct evidence for an age-related decline in the regenerative capacity of dystrophic muscle in response to noxious stimuli. We have compared the regenerative response of skeletal muscles from young (2 month old) and old (12 month old) normal and dystrophic (dy2J/dy2J) mice. Regenerating fibers, identified using antibodies specific for embryonic myosin heavy chain, were numerous in muscles from young dystrophic mice but rare in muscles from old dystrophic animals. Five days after a freezing injury a large number of regenerating fibers were identified at the site of the lesion in both young and old normal mice. In contrast, the regenerative response of dystrophic muscles varied strikingly with age and an abortive muscle regeneration was seen in old dystrophic animals. These results can be accounted for by a progressive age-related decline in the replicative capacity of dystrophic satellite myoblasts. © 1993 Accademia nazionale dei Lincei.