Analysis of NKs status revealed that the AA group had a smaller fraction of the CD56bright NK1 population and expanded late low-cytotoxic NK subsets than the YA group. Notably, NKs in the AA group had increased expression of DDIT4, ISG20, and CASP4 and decreased expression of DDX17, PCBP1 and TRIM56 (Figs. 3A, S6A; Table S8A–C). These genes were mostly enriched in apoptotic signaling pathways and cellular responses to lipopolysaccharide, along with decreased virus defense responses (Fig. S6I and S6J). As for BCs, we found increased expression of JUNB, IGHA1, SSR4 and CXCR4, indicative of increased memory BC signature and activity during aging (Figs. 3A, S7A; Table S9A–D). Moreover, the comparative functional analysis of aging-associated DEGs revealed that Naive BC in the AA group had increased cytokine-mediated signaling pathways (Fig. S7B). Additionally, analysis of downregulated DEGs and pathways in the AA group demonstrated that BCs were associated with reduced viral defense responses (Fig. S7C). These results indicate that NKs and BCs lose their capacity for antiviral activity with upregulated inflammatory states in aging.