Lynx1 regulates nAChRs to preserve the structure and function of neuromuscular synapses during aging

Nicotinic acetylcholine receptors (nAChRs) undergo aberrant changes in diseases and with advancing age that compromise the structure and function of neuromuscular junctions (NMJs). Despite this recognition, the mechanisms that regulate muscle nAChRs remain poorly understood. Here, we ask if Lynx1, shown to regulate nAChRs in the brain, plays a similar role at NMJs. We show that Lynx1 concentrates in the postsynaptic region of NMJs where it modulates the function and stability of nAChRs in young adult mice. However, Lynx1 levels decrease at aged NMJs suggesting roles in synaptic maintenance. Supporting this possibility, deletion of Lynx1 prematurely and progressively increases the incidence of NMJs with age-related features, culminating in the atrophy of muscle fibers. These data show that by promoting homeostatic synaptic plasticity and NMJ remodeling, Lynx1 regulation of nAChRs mitigates age-related damages at NMJs.