Immunodeficiency: primary or acquired
Aging has a profound impact on immune cell functions. Similarly, sex affects immune cell responses, disease susceptibility, severity, and symptoms. However, it is not well understood how sex and age together impact human immune system. To systematically study this, we generated flow cytometry, ATAC-seq, and RNA-seq maps from peripheral blood mononuclear cells (PBMCs) of healthy individuals (58 women, 50 men) across the adult lifespan (ages 22-93). Epigenomes/transcriptomes of PBMCs went through significant changes with aging. Some of these changes were shared between men and women (e.g., declines in T cell-associated loci), whereas others were sex-specific (male-specific decline in B cell-associated loci). Furthermore, trajectory and differential analyses revealed that male immune system age faster and more severely (e.g., magnitude of changes) and sooner than female immune system. Finally, unexpectedly, genomes of male and female PBMCs diverged over time, where old women had more active epigenomes/transcriptomes for adaptive cells compared to more activity for innate cells in older men, suggesting a more severe aging signature for men. Together these multi-faceted data provide a precise description of how aging affect immune system of men and women.