Statistically, women live longer than men. In France, in 2020, life expectancy at birth reached 85.1 years for women compared to 79.1 years for men, a gap of six years. In addition to this longevity advantage, women are more resilient to most health threats and benefit more from vaccines. This phenomenon is largely explained by a more efficient immune system than that of men. This gap is found all over the world, throughout the ages, but how can we explain it?
Recent research in immunology, virology and genetics, relayed by New Scientist, is beginning to reveal the causes of this biological superiority. Hormones and XX sex chromosomes play a key role in the activation of immune cells, which detect, fight and remember pathogens better than in men.
Scientific studies have shown that the majority of this immune advantage resides in the female sex chromosomes. As Duygu Ucar, an immunologist at the Jackson Laboratory in Connecticut (United States), explains, the X chromosome carries many genes related to immunity and having two copies of this chromosome provides additional protection.
Women therefore benefit from greater genetic diversity, their receptors reacting more quickly and more effectively to a wide range of pathogens: their bodies detect infections earlier and thus gain the advantage. It could also explain why women are about 20 percent less likely to develop most cancers, with cancer cells often losing function in genes that normally suppress tumors.
The key role of estrogen
Some of these genes are located on the X chromosome: if one of them has an abnormality, the second copy can correct the error. Conversely, certain male genetic profiles, including a particular lineage of the Y chromosome in men of European ancestry, increase the risk of coronary heart disease due to excessive inflammation and a diminished immune response. Additionally, a gene called UTY appears to make some men more vulnerable to complex immune-related diseases.
Female hormones also play a considerable role. Estrogen, in particular, strengthens both innate immunity (the body’s first line of defense) and adaptive immunity (memory acquired over time), activating cells such as neutrophils, which are essential for eliminating infectious agents. The work of Sarthak Gupta (National Institutes of Health, United States) highlights that estrogen potentiates these killer cells and optimizes the immune response.
In addition, estrogen stimulates the production of B lymphocytes, fundamental cells of the humoral response which produce antibodies and consolidate immune memory. In many species, females retain this memory longer than males – a major evolutionary advantage. This could also explain the better vaccine response in women.
Biomedical research nevertheless suffers from a lack of attention to these female specificities. Historically, study models have mainly been based on male biology, as Caroline Duncombe (Stanford University, California) points out. “Biological sex remains one of the major factors influencing health and disease throughout life, as it impacts genetics, hormones, lifestyle and environment”she specifies. This bias represents a challenge for both women and men: delving into female immune mechanisms could open up new therapeutic avenues for both sexes.
