Age-related increase in soluble and cell surface-associated neurite-outgrowth factors from rat muscle

While the number of nerve terminals per endplate decreases with age in the rat extensor digitorum longus (EDL) muscle, the number of endplates exhibiting ultraterminal sprouting, characteristic of denervation, increases. To determine if these changes associated with aging are accompanied by alterations in the production of muscle-derived neurite-outgrowth factors, we examined the effects of soluble and cell surface-associated components from innervated and denervated 10- and 25-month rat EDL muscles on a motoneuron-enriched fraction of embryonic chick spinal cord cells in vitro. Cells were cultured for 72 h with muscle extract or on muscle cross-sections. While soluble components of the extract affected initiation of neurite outgrowth, muscle cell surface-associated molecules influenced neurite elongation. Both muscle extract and muscle cross-sections from 10-month denervated animals were more effective in promoting neurite outgrowth than 10-month innervated muscle. There was no difference between 25-month innervated and 25-month denervated muscle. However, 25-month innervated and denervated muscles were significantly more effective in promoting neurite outgrowth than 10-month innervated muscle, but not different from 10-month denervated muscle. These results suggest that an age-related increase in muscle-derived soluble and cell surface-associated neurite-outgrowth factors may contribute to denervation-like morphological changes associated with aging at the neuromuscular junction.