Structural molecule–associated protein changes in SUMO1-deficient mice are associated with attenuated age-related anxiety-like behavior

SUMO1 is essential for normal neural function, yet its role in age-related behavioral changes remains unclear. Using open-field and three-chamber tests in adult and middle-aged female mice, we found that SUMO1 deletion attenuates age-related increases in anxiety-like behavior, whereas sociability is reduced independent of age. Proteomic profiling comparing middle-aged and adult SUMO1-KO mice identified 420 upregulated and 239 downregulated proteins, with enrichment in ribosomal function, synaptic signaling, extracellular matrix organization, and calcium homeostasis. Four structural molecule–associated proteins (Adora2a, Rpl14, Actg1, and Hapln2) exhibited age-related expression changes selectively in SUMO1-KO mice, as confirmed by western blot. These data indicate that SUMO1 deletion is associated with altered structural protein networks that coincide with modified anxiety-related aging trajectories. However, mechanistic links remain unresolved. Future studies using targeted pharmacological or genetic perturbations will be needed to determine whether and how these protein changes contribute to SUMO1-related behavioral alterations.