Due to technical limitations, high-dimensional molecular profiles in aging for rare cells such as DCs are lacking. Here, we overcame this challenge with a novel single-cell method. Aging increased the percentage of cDC2 cells and decreased the percentage of pDCs that engage antiviral activities by priming CD8+ TCs. By comparison, aging decreased the expression of CLEC12A, TXNIP, AHR and MALAT1 and increased the expression of HLA-DQA2 and IFN-stimulated genes. CLEC12A (Hutten et al., 2016) and TXNIP (Son et al., 2008) are critical for the antigen-presentation function of DCs, whereas MALAT1 and AHR are critical for tolerogenic DC differentiation (Takenaka and Quintana, 2017; Wu et al., 2018), and their dysregulation hampers DC function. Interestingly, HLA-DQA2 and IFN-stimulated genes were distinctly expressed in the cDC2 subset during aging. Moreover, our functional analysis of DEGs indicates that the aging of DCs was associated with a decrease in the antigen-presenting ability and an increase in activation of inflammatory signaling pathways, such as the response to hypoxia and IFN signaling. These findings highlight how aging affects DCs composition and function.