Limited Activity‐Dependent Changes in NMJ Structure and Function During Aging

Abstract

Aging has been associated with losses of muscle mass and strength, a phenomenon termed “sarcopenia”. A growing body of evidence suggests that it may originate from alterations (mostly structural fragmentation) of neuromuscular junctions (NMJs). Furthermore some evidence show that physical activity partially prevents age‐related NMJs fragmentation and muscle mass and strength losses, reinforcing the relationship between NMJs and muscle function. However, the efficacy of the NMJ, that is, the ability of the motor neuron to control the muscle fiber, has been largely overlooked. Hence, we investigated NMJ synaptic strength and plasticity, two important indicators of its function. We compared soleus muscles of active adult (12 months) and active old mice (30 months). NMJ structure was assessed by immunolabeling while synaptic properties were studied using electrophysiological recordings. Despite their activity level, soleus muscle mass was lower in older than in young mice (17.9±0.4 mg vs. 22.2±0.3, respectively, p<0.001). Endplates of NMJs of old mice were also more fragmented (6.2±0.3 vs. 1.9±0.2 fragments, p=0.0023). Furthermore, while a high frequency stimulation (60Hz, 30s) resulted in a long‐lasting potentiation in adults (4±2%), it produced a long‐term depression in old mice (−8±2%, p=0.039, 40 min post‐stimulation). However, synaptic strength (Quantal content; the amount of vesicle of neurotransmitters released during a stimulation) was preserved in old mice (3.2±0.3 vs. 3.1±0.2 in young mice, p=0.63). Results suggest that activity reduces some aspects of NMJ aging (structure and synaptic strength). However, other aspects (synaptic plasticity) remained altered, suggesting that they may be implicated in the remaining loss of muscle mass and strength in active elderly.