Aging normal and dystrophic mouse muscle: analysis of myogenicity in cultures of living single fibers.

In the early stages of Duchenne muscular dystrophy, chronic muscle degeneration is counterbalanced by regeneration whose progressive failure beyond the fifth year is attributed to an accelerated senescence associated with excessive myogenic cell division. This idea was tested by counting the numbers of myogenic cells accumulating over 90 h around individual living fibers isolated from muscles of dystrophic (mdx) and normal mice, 14-550 days of age. In cultures of normal muscle fibers, the number of myogenic cells per fiber decreased with increasing age of the animal. Cultures from young mdx mice exhibited an age-related increase in myogenic cell number, attaining at 50 days three times the number in control cultures. Thereafter, myogenic cell number progressively declined with animal age to control values. Thus, there is no evidence that extensive myoblast proliferation in young dystrophic mice-and, by association, in Duchenne muscular dystrophy patients-depletes their myogenic responsiveness in later life when they become weak and wasted.

Role of weight-bearing function on expression of myosin isoforms during regeneration of rat soleus muscles.

The expression of myosin isoforms was studied in regenerated rat soleus muscle during either normal or altered postural activity. Regeneration was induced following injury by venom from the Notechis scutatus scutatus snake. Immunohistochemical analysis showed that, in regenerating soleus muscle after 3 wk of hindlimb suspension, nearly all fibers reacted positively with the myosin heavy chain (MHC) antibody associated with fast-twitch muscle fibers (fast MHC). When 3 wk of recovery with normal weight-bearing activity followed hindlimb suspension, the regeneration soleus muscle exhibited a nearly homogeneous staining with the MHC antibody associated with the slow-twitch muscle fibers (slow MHC). These findings were in accordance with quantitative analysis of the electrophoretic separation of the native myosin isoforms. Immunohistochemical data showed that removal of weight bearing in the 21-day old regenerated soleus muscles resulted in an increase in fast MHC expression. Together, the results of the present study clearly demonstrate that the postural load is an important component in the induction of slow MHC in regenerating muscle and that the control of the expression of MHC in muscle comprising a homogeneous population of fibers deriving from satellite cells appears more homogeneous and more complete than in a nondegenerated one.