Firstly, we demonstrated using KEGG signaling pathway clustering that age-related proteomic changes in the hypothalamus were potentially associated with neurodegenerative phenotypes (Alzheimer's disease, Parkinson's disease, Huntington's disease), cognitive and neurodevelopmental function (axon guidance, long-term potentiation, Notch signaling, Wnt signaling pathway), dysglycemia (Type II diabetes mellitus, insulin signaling), and neuronal cytoskeletal remodeling (Focal adhesion, Gap junction, Regulation of actin cytoskeleton) (Fig. 3). Here, INS is linked to type 2 diabetes mellitus.