Remodeling of the neuromuscular junction precedes sarcopenia related alterations in myofibers

Abstract

Several mechanisms contributing to the etiology of sarcopenia (age-related loss of muscle size) have been postulated. One of these attributes the loss of muscle mass to a preceding age-related denervation of myofibers. The aim of this study was to determine if signs of denervation were apparent at the neuromuscular junction (NMJ) before fiber atrophy, or fiber type conversion could be documented, and to reveal if a muscle's activity level impacts its sensitivity to age-related denervation. Plantaris and soleus muscles were obtained from young adult (10 months) and early aged (21 months) rats. Pre- and post-synaptic NMJ morphology was quantified with cytofluorescent staining of nerve terminal branches and endplate regions, respectively. Myofiber profiles (fiber size and fiber type composition) were assessed with histochemical procedures. Results show that in the lightly recruited plantaris, significant (P<0.05) signs of denervation were noted in aged rats, while the same muscles displayed no change in myofiber profile. In the heavily recruited soleus, however, there was little evidence of denervation, and again no alterations in myofiber profile. These results indicate that age-related denervation occurs before myofiber atrophy, and that high amounts of neuromuscular activity may delay the onset of age-related denervation and sarcopenia.

Figure 1

Representative image of fluorescently stained pre-synaptic nerve terminal branching (left panel), and fluorescently stained post-synaptic acetylcholine receptors (right panel) of the same NMJ. Original magnification of X 1000.

Figure 2

Sample of myofibers histochemically stained for myosin ATPase activity following acidic pre-incubation. Darkest myofibers are type I, lightest myofibers are type IIA, and intermediately stained myofibers are type II X/B. Original magnification of X 400.