Aging alters mechanisms underlying voluntary movements in spinal motor neurons of mice, primates and humans.
Spinal motor neurons have been implicated in the loss of motor function that occurs with advancing age. However, the cellular and molecular mechanisms that impair the function of these neurons during aging remain unknown. Here, we show that motor neurons do not die in old female and male mice, rhesus monkeys, and humans. Instead, these neurons selectively shed excitatory synaptic inputs throughout the soma and dendritic arbor during aging. By examining the translatome , we also show that aging alters the molecular composition of motor neurons in both male and female mice. Aging motor neurons present with changes in genes and molecular pathways with roles in glia-mediated synaptic pruning, and inflammation. They also exhibit changes in pathways with roles in axonal regeneration caused by axotomy and Amyotrophic Lateral Sclerosis (ALS). Thus, we have identified cellular and molecular mechanisms altered in aged motor neurons that could serve as therapeutic targets to preserve motor function during aging. Overall design: RNA bound to Hemagglutinin-tagged ribosomal protein L22 (HA-RPL22) was co-immunoprecipated from the spinal cords of male 3, 12, 18 and 24 month-old and female 3, 12 and 18 month old Chat-Cre; Ribotag mice in which HA-RPL22 is conditionally expressed under the choline acetyl transferase (ChAT) promoter to enrich for motor neuron transcripts.