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Free grafts of the extensor digitorum longus (EDL) muscle in 4-month-old rats regenerate 2-3 times better than in 24-month-old rats. Based on these data, we formulated the working hypothesis that deficient reinnervation is one of the most important age-related environmental factors within the host that might account for the poor regeneration. In the present experiments, we compared the regeneration of EDL muscles in two groups of young and old rats: (a) 21-day grafts, with fibers regenerating in the absence of nerves, and (b) Marcaine-treated muscle with fibers regenerating in the presence of uninterrupted innervation. The specific hypothesis was that, under each of these circumstances, reinnervation was not involved and age-related differences in regeneration would not be seen. Differences were assessed by measurements of mass and maximum isometric force normalized to values for age-matched control muscles. In the absence of nerves, the degree of regeneration in 21-day noninnervated EDL grafts was not significantly different between young and old rats. Similarly, when EDL muscles were damaged by Marcaine and regenerated in the presence of uninterrupted innervation, no differences were noted between young and old rats. These data support the working hypothesis that a deficiency in reinnervation with increasing age accounts, at least in part, for the poorer success of muscle regeneration in grafts in old compared with young rats.

The Regeneration of Noninnervated Musele Grafts and Marcaine-Treated Muscles in Young and Old Rats