BSC researchers Aida Ripoll-Cladelles (left), Marta Melé (center) and Maria Sopena-Rios (right) in front of MareNostrum 5 supercomputer. Credit: Mario Ejarque/BSC-CNS
Statistics show clear differences in the immune system according to sex: men are more susceptible to infections and cancers, while women have stronger immune responses, which translate, for example, into better responses to vaccines. Even so, with a more reactive immune system, the probability of the body attacking itself also increases, causing 80% of autoimmune disease development to occur in women.
A new study has demonstrated, for the first time, the cells and genes responsible for these differences.
Published in Nature Aging, the results show that women present more pronounced changes in the immune system with age, with an increase in inflammatory immune cells. This finding could help explain why autoimmune diseases are mainly developed by women, especially at advanced ages, as well as the worsening of certain inflammatory pathologies after menopause.
On the other hand, the changes associated with immune system aging observed in men are globally less extensive, but an increase in certain blood cells presenting pre-leukemia alterations was observed—a fact that could explain why some blood cancers are more frequent in older men.
“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,” said Maria Sopena-Rios, first co-author of the study. “With cell-by-cell analysis and a much larger sample, we were able to detect these patterns and compare them robustly between biological sexes.”
In the laboratory, the team used single-cell RNA sequencing to analyze blood samples from nearly 1,000 people of different ages covering the entire adult life. In total, the researchers analyzed the activity of 20,000 genes in more than 1 million blood cells.
Empirically, the team relied on the MareNostrum 5 supercomputer at the Barcelona Supercomputing Center to manage, process and analyze the resulting volume of data.
With these discoveries, the study establishes the bases for incorporating biological sex as a key variable in precision medicine for aging. The identification of sex-specific aging cells and biomarkers opens the door to the development of preventive, diagnostic and therapeutic strategies better adapted to each sex.
Data from Barcelona Supercomputing Center