Age-Associated Dysregulation of Postsynaptic Mitochondria Perturbs Reinnervation Kinetics.

ABSTRACT: Age-associated degeneration of neuromuscular junctions (NMJs) contributes to sarcopenia and motor function decline, yet the mechanisms that drive this dysfunction in aging remain poorly defined. Here, we demonstrate that postsynaptic mitochondria are significantly diminished in quantity in old-aged skeletal muscle, correlating with increased denervation and delayed reinnervation following nerve injury. Single-nucleus RNA sequencing before and after sciatic nerve crush from young and old-aged muscles further revealed that sub-synaptic myonuclei in old-aged muscle exhibit attenuated expression of mitochondrial gene programs, including oxidative phosphorylation, biogenesis, and import. To test whether these deficits are causal, we developed a muscle-specific CRISPR genome editing approach and

SUBMITTER: Guzman SD 

PROVIDER: S-EPMC12775679 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature