A new study shows that aging affects the immune system differently in women and men, with women experiencing more pronounced changes over time.

It has long been known that immune responses vary by sex: men are generally more vulnerable to infections and cancer, while women tend to mount stronger immune defenses and respond better to vaccines. However, this heightened reactivity also increases the risk of autoimmune diseases, around 80% of which occur in women.

Researchers from the Barcelona Supercomputing Center (BSC-CNS) have now provided the first detailed molecular explanation of how immune aging differs between sexes. Their findings, published in Nature Aging, reveal that women undergo more significant age-related immune changes, particularly an increase in inflammatory immune cells. This may help explain why autoimmune conditions are more common in women, especially later in life, and why inflammatory diseases often worsen after menopause.

In men, age-related immune changes were less extensive overall. However, scientists observed an increase in certain blood cells with pre-leukemic features, which could partly explain the higher incidence of some blood cancers among older men.

The study analyzed blood samples from nearly 1,000 individuals across the adult lifespan. Using single-cell RNA sequencing, researchers examined over one million blood cells and tracked the activity of around 20,000 genes. This approach allowed them to map how immune cells evolve with age and identify clear sex-based differences.

According to co-author Maria Sopena-Rios, earlier studies often relied on averaged data from many cells, making it difficult to detect gradual aging effects. By analyzing cells individually and using a large dataset, the team was able to uncover more precise patterns and compare them reliably between sexes.

The scale and complexity of the data required advanced computational tools, including the MareNostrum 5 supercomputer, which played a crucial role in processing and analyzing the results.

The researchers also emphasized the importance of including sex as a biological variable in scientific studies. Historically, women have been underrepresented in research, limiting understanding of sex-specific health differences. This study, which used a balanced dataset of men and women, highlights how critical such inclusion is.

The findings pave the way for incorporating sex differences into precision medicine. Identifying sex-specific immune aging patterns and biomarkers could lead to more personalized approaches in prevention, diagnosis, and treatment, ultimately improving health outcomes for both women and men.