Neuromuscular Junction Plasticity Confers Atrophy Resilience of Aging Muscle

Abstract

INTRODUCTIONAging is associated with progressive muscle atrophy that contributes to weakness and increased risk of falls in advanced age. Our previous work has highlighted the importance of persistent denervation of muscle fibers (Rowan et al. PLoS One 2012), associated with a failed reinnervation response (Aare et al. Skeletal Muscle 2016), as a primary cause of muscle fiber atrophy in advanced age. We have also noted previously (Picard et al. Aging Cell 2011) that there is considerable heterogeneity between different muscles in severity of atrophy with aging that is unrelated to muscle fiber type composition per se. Most notably, in a comparison of two hindlimb muscles predominately composed of type I fibers in young adulthood, the soleus (Sol) exhibits a 30–40% decline in muscle mass while the adductor longus (AL) exhibits a remarkable 47% increase in muscle mass in advanced age rats. In view of the importance of denervation to aging muscle atrophy, we compared age‐related changes in neuromuscular junction (NMJ) morphology in the Sol and AL muscles to test the hypothesis that vulnerability to aging muscle atrophy parallels adaptive plasticity of the NMJ with aging.FINDINGSAL and Sol muscles were collected from 9‐mo old (YA) and 34‐mo old (VO) male Fischer 344 × Brown Norway F1‐hybrid (F344BN) rats (n=6; 3 YA) obtained from the colony maintained by the National Institute on Aging. NMJs in each muscle were immunofluorescently labelled and imaged by confocal microscopy (Leica SP8). Images were quantitatively assessed using NMJ‐Morph, an Image‐J based package designed for characterization and analysis of NMJ morphology. Interestingly, whereas for several parameters of NMJ morphology the AL exhibited changes with aging that were either not seen in the Sol or of greater magnitude in the AL, the majority of these parameters were already altered in the YA Sol versus the YA AL in the same direction as occurred with aging in the AL. As such, this suggests that NMJ morphological plasticity may be initiated much earlier in the lifespan in the Sol and that exhaustion of this plasticity may account for the atrophy susceptibility of the Sol in advanced age. Further to this, our data suggest that a substantial reserve of NMJ plasticity in the AL is amongst the factors responsible for its resilience to aging muscle atrophy in advanced age.CONCLUSIONOur results are consistent with the hypothesis that vulnerability to aging muscle atrophy parallels adaptive plasticity of the NMJ with aging.Support or Funding InformationSSB is supported by a T32 from the National Institute of Child Health and Human Development Grant T32HD043730.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.