Aging is a process that leads to the deterioration in physiological functioning of the brain. Prior research has proposed that hippocampal aging is accompanied by genetic alterations in neural, synaptic, and immune functions. Nevertheless, interactome-based interrogations of gene alterations in hippocampal aging, remain scarce. Our study integrated gene expression profiles of the hippocampus from young and aged rats and functionally classified network-mapped genes based on their interactome. Hippocampal differentially expressed genes (DEGs) between young (5–8 months) and aged (21–26 months) male rats (Rattus norvegicus) were retrieved from five publicly available datasets (GSE14505, GSE20219, GSE14723, GSE14724, and GSE14725; 38 young and 29 aged samples). Encoded hippocampal proteins of age-related DEGs and their interactome were predicted. Clustered network DEGs were identified and the highest-ranked was functionally annotated. A single cluster of 19 age-related hippocampal DEGs was revealed, which was linked with immune response (biological process, P = 1.71E-17), immunoglobulin G binding (molecular function, P = 1.92E-08), and intrinsic component of plasma membrane (cellular component, P = 1.25E-06). Our findings revealed dysregulated hippocampal immunoglobulin dynamics in the aging rat brain. Whether a consequence of neurovascular perturbations and dysregulated blood-brain barrier permeability, the role of hippocampal immunoregulation in the pathobiology of aging warrants further investigation.