In this study, we investigated the molecular changes of age-related splenic tissues, including 6 weeks and 20 months old, by RNA-seq and bioinformatics methods. Meanwhile, a transcriptomic dataset GSE73450 was downloaded from GEO database to explore the differentially expressed genes (DEGs) in aging. Ultimately, the integrated analysis of RNA-seq and GEO database gene chips provides further meaningful insights to comprehensively explore the molecular mechanisms of immune senescence.