The evidence for old age motor neuron death: A scoping review

Age-related neuromuscular dysfunction is widely recognized; however, the extent to which aging is accompanied by motor neuron (MN) loss remains underexplored. This review evaluates evidence for MN loss with aging across species and anatomical motor pools. We synthesize PUBMED studies in humans, non-human primates, rats and mice within the spinal cord and brainstem. Attention was given to the methodological approach used to quantify MNs and categorized based on what MNs were quantified (specific pools, vertebral levels, lateral motor columns). Methods were assessed qualitatively, based on stereological and non-stereological density counting approaches, and the staining techniques identified as optimal or suboptimal by defined criteria. To facilitate cross-study comparison we conducted quantitative assessments including: coefficients of variance, percentage differences between groups and standardized effect sizes calculated with Cohen's d. Across species and anatomical regions, the overall literature supports the presence of age-related MN loss. Evidence is strongest in studies using robust counting approaches such as stereology, and appropriate MN markers. As age-related MN degeneration is more heavily investigated and becomes a locus of intervention, future work must employ rigorous methodological standards to accurately determine the extent, regional specificity, and functional consequence of aging MN loss.