Comprehensive transcriptomic profiling reveals impaired polyamine metabolism as a contributor to age-related muscle decline.

Here, we present a spatial transcriptomic atlas of skeletal muscle from young and aged mice, resolving age-associated transcriptional reprogramming across distinct myofiber types and tissue compartments. Our analyses uncover coordinated alterations in sarcomeric organization, excitation-contraction coupling, and oxidative stress responses, together with fiber type-specific metabolic rewiring toward glycolytic or oxidative programs.

We also delineate conserved molecular signatures across muscles and species, highlighting Car3 as a potential pan-muscle biomarker of sarcopenia. In this context, we identify selective downregulation of key enzymes in the polyamine biosynthetic pathway, including Amd1 and Smox, resulting in reduced spermidine levels in aged muscle. This decline in polyamine availability also impacts muscle-resident cell populations.