Remodeling of the immune system across human lifespan at single cell resolution. Homo sapiens

The immune system is dynamic and changes throughout life, yet molecular cellular details of these changes are not well characterized. To precisely characterize age and sex associated changes in peripheral immune cells throughout lifespan, we profiled more than 600K cells from 95 samples from four age groups: infants (n=27, 2-18 months old), children (n=23), young adults (n=18), and older adults (n=27, 65-90+ years old) using single cell RNA-seq. CD8pos T cells were the most affected with age, where naive T cells declined and cytotoxic GZMKpos and TEMRA cells expanded with age. The level of cytotoxicity also increased within these populations with age. Myeloid cells significantly expanded with age. Interestingly sex differences in myeloid cells also increased with age; older men had more monocytes and DCs compared to older women. B cells are also affected both with age and sex, as expected, there was a switch from naive to memory B cells with age. More unexpectedly, older women had more memory and translational B cells compared to older men. Infant immune cells were the most distinct both in terms of cell-compositional and cell-intrinsic profiles, driven by the expansion of naive cells and higher expression of Type I Interferon genes. Together these data precisely describe how age and sex affects immune cells across the human lifespan.This Lifespan study is a compilation of new (n=67) and existing participants (n=27) from 5 dbGaP studies. The raw data (fastq files) from participants HY13, HY18 and HY19 will not be included in the dataset per consent. HI17 and HI23 samples originate from the same infant collected at two time points (2 months for HI17 and 11 months for HI23).