By analyzing age-associated DEGs in CD4+ TCs, we found enrichment in inflammatory and effector genes (Tables S5A and 6A–E). To determine cell-subtype-specific gene signatures within different CD4+ TC subpopulations, we generated UpSet plots of upregulated DEGs in different CD4+ TC subsets. We found a range of subtype-specific patterns, including the IL2 receptor (IL2RA) in Naive cells, CCR10 in Tem, and GZMB and TRBV11-2 in Tex (Fig. 3E). GO and pathway analysis of the DEGs demonstrated that effector and memory subsets were most affected by aging based on the number of DEGs. For example, in CD4 Tem, TNF, interleukin signaling and apoptotic pathways were enhanced, whereas mRNA processing was impaired (Figs. 3F and S6C). Analysis of CD8+ TC status indicated that the AA group had increased expression of chemokines and granzyme family members (Fig. S6D; Tables S5B and 7A–D). Moreover, aging was associated with a decreased proportion of CD8 Naive with increased apoptotic signaling pathway and lymphocyte activation and an expanded CD8 Tem compartment with increased cytokine production as well as reduced chromatin remodeling and antiviral function (Fig. S6E and S6F). In addition, T-mito in aged group was associated with the upregulated inflammatory signaling molecules HLA-DRB5, PDCD5 and PSMA2 (Fig. S6G; Table S5C) and inflammatory pathways (Fig. S6H).