Study Reveals How Biological Sex Shapes Immune Aging

Sex-based differences in immune function are well known: men are generally more susceptible to infections and certain cancers, while women tend to mount stronger immune responses, including better vaccine outcomes. Yet, this heightened reactivity in women also raises the risk of autoimmune diseases, which account for about 80% of cases among females. Understanding how these differences evolve as the immune system ages has remained challenging—until now.

A study by the Barcelona Supercomputing Center – Centro Nacional de Supercomputación (BSC-CNS), published in Nature Aging, demonstrates that immune aging unfolds differently in men and women. The researchers identified the distinct cells and genes involved, providing a molecular basis for sex-related disparities long observed across populations. Their results show that women experience more marked immune changes with age, with a rise in inflammatory cell types. This finding may help clarify why autoimmune disorders become more common among older women and why inflammatory conditions tend to worsen after menopause. Meanwhile, men show fewer overall immune alterations but an increase in blood cells with pre-leukemic traits, offering insight into the higher incidence of certain blood cancers in aging men.

The analysis drew on blood samples from nearly 1,000 adults of varying ages, examined using single-cell RNA sequencing technology that enables gene-level study of individual cells. In total, the researchers assessed over one million blood cells and 20,000 genes, revealing clear sex-related patterns in how the immune system changes over time. “Until now, most studies analyzed the immune system based on the average of many cells at once, which makes it difficult to capture the progressive effects of aging. With cell-by-cell analysis and a much larger sample, we were able to detect these patterns and compare them robustly between biological sexes,” explained Maria Sopena-Rios, first co-author of the study.

“Many studies still do not take sex into account in their analyses, or directly only use data from men, so they leave key questions unanswered. Our research was born precisely from this need and combines a scientific outlook with a sex perspective, inclusive data, and great computational power,” highlighted Marta Melé, director of the study.