Abstract / Description
The dynamic changes in immune cell composition throughout the human lifespan remain poorly understood. Here, we performed single-cell RNA sequencing and single-cell assay for transposase-accessible chromatin sequencing on peripheral blood mononuclear cells from healthy donors, spanning mid-fetal to late adulthood. Our findings revealed age-associated reprogramming across lymphoid and myeloid lineages, with T cells undergoing the most significant transcriptional remodeling. Notably, ITGB1CD8 effector memory T cells played a protective role in young adulthood. Furthermore, an immunosuppressive AREG natural killer (NK) cell subset was enriched in early childhood, exhibiting low expression of cytotoxic and activating markers and high expression of inhibitory molecules. Additionally, fetal-derived XCL2CD56 NK cells show an upregulation of inhibitory receptor KLRC1, while IL1B monocytes increased in aging, contributing to inflammaging. Overall, our study provides a comprehensive single-cell atlas of peripheral immune cell dynamics across the human lifespan and reveals various age-related signatures, offering insights into immune aging and its role in age-related diseases.