Seminal studies have provided insights into the compositions and functional alterations occurring during aging, primarily based on previously described markers detected in pooled heterogeneous cell populations. The recent development of unbiased high-throughput single-cell technologies with high accuracy and specificity has begun to change immunological studies, as researchers worldwide are ushering in the new field of systems immunology. By using single-cell sequencing, recent studies have reported that cell-to-cell transcriptional variability increases with age in CD4+ TCs (Bahar et al., 2006; Martinez-Jimenez et al., 2017) and in leukocytes from old mouse lungs (Angelidis et al., 2019). Aging also increases the variations in chromatin modifications of human immune cells (Cheung et al., 2018). Very recently, many immunological phenotypes, such as intratissue accumulation of proinflammatory cells, have been reported in aging rodent and primate models (Messaoudi et al., 2006; Watson et al., 2017; Hammond et al., 2019; Ma et al., 2020). However, a comprehensive aging cell atlas of human peripheral blood that systematically connects all the blood lineages and cell subtypes has not yet been constructed.