Integrated single-cell sequencing analysis reveals peripheral immune landscape across the human lifespan

Systematic understanding of immune dynamics across the entire human lifespan at single-cell resolution is currently lacking. Here, we performed single-cell RNA sequencing (scRNA-seq) and single-cell T cell receptor (TCR)/B cell receptor (BCR) sequencing (scTCR/BCR-seq) on over 380,000 peripheral blood mononuclear cells collected from 45 healthy participants aged 0 to over 90 years. We revealed that the functions of T cell subsets were most susceptible to senescence among all PBMCs, featured by increased NF-κB signaling and IFN-γ responses pathways, while reduced telomere maintenance and energy metabolism. By combined analysis of scRNA-seq and scTCR-seq, we revealed that 1) Naïve CD4+ T and naïve CD8+ T cells displayed different aging patterns in both transcriptomes and immune repertoires; and 2) CD8+ MAIT cells showed a higher cell abundance and clonal diversity in adolescents. In summary, our work provided valuable insights and rich resources for understanding the development and aging of the human immune system across the lifespan. ### Competing Interest Statement The authors have declared no competing interest.