Sexual-dimorphism in human immune system aging

TLDR

Sex differences in immune function underlie health and lifespan disparities, yet how sex influences immune aging remains unclear. The study profiled peripheral blood mononuclear cells from 172 healthy adults aged 22–93 using ATAC‑seq, RNA‑seq, and flow cytometry. Epigenomic aging signatures show declining naïve T cells and rising monocyte and cytotoxic activity, with larger magnitude in men, a male‑specific B‑cell locus loss, two age‑related spikes (late‑thirties common to both sexes, an earlier, stronger spike in men), and post‑65 increases in men’s innate/pro‑inflammatory activity and reduced adaptive responses, all visualized at the provided portal.

Abstract

Differences in immune function and responses contribute to health- and life-span disparities between sexes. However, the role of sex in immune system aging is not well understood. Here, we characterize peripheral blood mononuclear cells from 172 healthy adults 22-93 years of age using ATAC-seq, RNA-seq, and flow cytometry. These data reveal a shared epigenomic signature of aging including declining naïve T cell and increasing monocyte and cytotoxic cell functions. These changes are greater in magnitude in men and accompanied by a male-specific decline in B-cell specific loci. Age-related epigenomic changes first spike around late-thirties with similar timing and magnitude between sexes, whereas the second spike is earlier and stronger in men. Unexpectedly, genomic differences between sexes increase after age 65, with men having higher innate and pro-inflammatory activity and lower adaptive activity. Impact of age and sex on immune phenotypes can be visualized at https://immune-aging.jax.org to provide insights into future studies.