Differential changes in the end-plate architecture of functionally diverse muscles during aging

Architectural changes at the neuromuscular junctions of three functionally diverse muscles, the diaphragm, extensor digitorum longus (EDL), and soleus, were studied in rats from adulthood (10 mo) through senescence (31 mo). End-plate structure was examined using a silver-gold impregnation of the axon and its terminal arborization. The mean number of terminal branches per end plate, including those that appeared to exhibit signs of sprouting or degeneration, were examined as a function of age. Nerve terminal branch length, the number of major myelinated axon branches per end plate, and end-plate area were also examined. To ascertain trends in the data, smoothing of mean values for time-series analysis was performed. Both fast-twitch diaphragm and EDL muscles revealed more pronounced fluctuations in nerve terminal branch number during aging than did the slow-twitch soleus. Smoothed trends of the mean number of nerve terminal branches per end plate show that nerve terminal proliferation increased with age at the diaphragm neuromuscular junction but decreased at the hindlimb junctions. Age-related changes in average terminal branch number progressed gradually in all muscles until 25 mo of age, after which we observed a precipitous increase at 28 mo and subsequent decline at 31 mo. Trends of change indicate that although sprouting within the diaphragm was maintained during aging, both EDL and soleus experienced a general decline in sprouting. Degeneration generally decreased at all nerve-muscle junctions with aging, although the decline began at a later age in the diaphragm. Analysis of mean data values indicates that in both the EDL and soleus, sprouting and degeneration attained minimum values at 25 mo of age. This was followed by a significant increase at 28 mo and then a decline by 31 mo of age. In general, sprouting fluctuated more severely than degeneration. We conclude that despite the variability from one age to the next, age-related trends of change are evident in nerve terminal branch number. The direction of these changes appears to be influenced by the degree to which muscle activity is maintained during aging. However, regardless of functional status, all three muscles experienced dramatic changes in end-plate morphology after 25 mo of age.