Motor Unit Properties of Nerve-Intact Extensor Digitorum Longus Muscle Grafts In Young and Old Rats

Abstract

Impaired reinnervation has been implicated as the cause of the threefold disparity in the recovery of maximum force (P0) of standard muscle grafts in old compared with young rats. The specific, null hypothesis of this study is that compared with age-matched control extensor digitorum longus (EDL) muscles, nerve-intact EDL muscle grafts in young and old rats show no evidence of an age-related impairment in reinnervation. Nerve-intact grafts were performed in 3-month-old and 23-month-old rats and were evaluated 60 days postoperatively. Compared with age-matched control EDL muscles, nerve-intact grafts in young and old rats showed no difference in muscle mass or motor unit numbers. The mean motor unit P0 for nerve-intact graft muscles in both age groups was significantly lower than that of age-matched control muscles. These data support our hypothesis that if axons are allowed to regenerate in an endoneurial environment, there is no evidence of an age-related impairment in muscle reinnervation.

Cellular and molecular mechanisms underlying age-related skeletal muscle wasting and weakness

“…Classic experiments in mammalian muscle regeneration revealed that the reduced regenerative potential of cross-transplanted muscle grafts was dictated largely by the age of the host rather than of the donor Faulkner 1989, 1996;Cederna et al 2001). More recently, this effect was confirmed in a model of parabiosis where young and old mice had a shared circulation (Conboy et al 2005).…”

Neural control of aging skeletal muscle

“…Lack of nerve damage provided favourable conditions for muscle regeneration, together with an age-related effect of the local environment on the transplants . As evidence of the importance of neural factors in nerve regeneration, the same group reported that when axons are allowed to regenerate in an endoneurial environment, there is no evidence of age-related impairment in muscle re-innervation (Cederna et al ., 2001). In summary, although old muscle is capable of regeneration similar to that of young muscle, the presence of an intact nerve supply appears to be critical to recovery, together with less clearly defined factors associated with the local environment.…”

Skeletal Muscle Plasticity in Health and Disease

“…The myelin sheath of peripheral nerves deteriorates due to a demyelination and remyelination process that causes wide incisures and infolded or outfolded myelin loops resulting in morphological irregularities with age (Ceballos et al, 1999). This process may impede reinnervation of denervated muscle fibers due to a reduction in the endoneurial conduits for axonal regeneration (Cederna et al, 2001). In fact, nerve-intact EDL autotransplants, in which the neural sheath is still intact, allow re-innervation, and thus, regeneration of muscle fibers to occur in both young and old rats (Cederna et al, 2001).…”

“…This process may impede reinnervation of denervated muscle fibers due to a reduction in the endoneurial conduits for axonal regeneration (Cederna et al, 2001). In fact, nerve-intact EDL autotransplants, in which the neural sheath is still intact, allow re-innervation, and thus, regeneration of muscle fibers to occur in both young and old rats (Cederna et al, 2001). In addition to the need for an axonal conduit, re-innervation requires anterograde axonal delivery of cytoskeletal proteins to the growing axon, many of which are transported in the "slow component b" (SCb) of anterograde axonal transport McQuarrie, 1991, 1993).…”