Statistics show clear differences in the immune system of the population according to gender. Men are more susceptible to infections and cancer, while women have a stronger immune response, making them more responsive to vaccines, for example. Still, as the immune system becomes more reactive, the body becomes more likely to attack itself, and 80% of autoimmune disease cases occur in women.
In this context, understanding the aging of the immune system is key. This is because as we age, the composition of our immune cells changes, reducing their defenses and making us more susceptible to disease. But until now it has been impossible to understand how sex influences this profound change.
New research by the Barcelona Supercomputing Center – Centro Nacional de Supercomputación (BSC-CNS) was published today. natural aging demonstrated for the first time that immunological aging follows different dynamics between men and women, identified the cells and genes involved in the process, and provided a molecular explanation for differences previously observed only globally within populations.
Therefore, the results reveal that women exhibit more pronounced changes in their immune systems with age, with an increase in inflammatory immune cells. The findings may help explain why autoimmune diseases primarily affect women, especially older women, and why certain inflammatory conditions worsen after menopause.
On the other hand, although the age-related changes in the immune system observed in men are less extensive overall, an increase in certain blood cells that exhibit pre-leukemic changes has been observed, a fact that may explain why some blood cancers occur more frequently in older men.
The discovery of these patterns was made possible thanks to a combination of analysis of blood samples from around 1,000 people of various ages, covering the entire adult life span, and a technique called single-cell RNA sequencing, which allows each cell to be analyzed individually. In total, the researchers analyzed the activity of 20,000 genes in more than 1 million blood cells, allowing them to determine how the immune system changes over time and detect clear differences between the sexes.
Until now, most studies analyzed the immune system based on averages of large numbers of cells at once, making it difficult to capture the progressive effects of aging. Cell-by-cell analysis and a much larger sample allowed us to detect these patterns and reliably compare them between biological sexes. ”
Maria Sopena-Rios, BSC researcher and first co-author of the study
Managing, processing and analyzing data of this scale required the scientific team to use advanced computational techniques never before applied to such complex datasets, using the MareNostrum 5 supercomputer as a key part of enabling research that would not have been possible without high-performance computing infrastructure.
Aging from a sexual perspective
The authors comment that although there is evidence that immune system aging differs by gender, women have traditionally been underrepresented in research. This was the first time that a large sample was analyzed with a balance of males and females, which was a crucial fact in obtaining these results.
“Many studies still do not take gender into account in their analyzes or only directly use data from men, leaving important questions unanswered. Our study is born out of precisely this need, combining a scientific perspective with a gender perspective, comprehensive data, and superior computational power,” emphasized Marta Mele, head of the Transcriptomics and Functional Genomics Group and research director at the BSC.
With these findings, this study established the basis for incorporating biological sex as an important variable in precision medicine for aging. Identification of sex-specific senescent cells and biomarkers opens the door to the development of preventive, diagnostic, and therapeutic strategies better suited to women and men, contributing to more personalized and equitable healthcare in an aging population.
“The immune system plays a fundamental role throughout the organism. Therefore, the differences we observed have very important general effects throughout the body. A deeper understanding of immune system aging will help us understand processes that affect multiple tissues beyond the blood,” said Ida Ripoll-Claderas, a BSC researcher and first co-author of the study.
The authors conclude that treating aging as a homogeneous process across a population hides important biological differences, and understanding how aging differs between women and men is essential to improving immune health and promoting healthy aging within everyone’s reach.
sauce:
Barcelona Supercomputing Center
Reference magazines:
Sopena Rios, M. others. (2026). Single-cell analysis of the human immune system reveals sex-specific immunosenescence dynamics. natural aging. DOI: 10.1038/s43587-026-01099-x. https://www.nature.com/articles/s43587-026-01099-x
