A growing body of research suggests that biological sex plays a significant role in how the immune system changes with age, influencing both disease risk and overall health outcomes in older adults.

A recent review examines how immune aging, driven by two key processes known as immunosenescence and inflammaging, differs between males and females. Immunosenescence refers to the gradual decline in immune function, while inflammaging describes a persistent, low-grade inflammatory state that develops with age. Together, these processes contribute to increased vulnerability to infections, cancer, and chronic age-related diseases such as atherosclerosis, dementia, and osteoarthritis.

The immune system itself is composed of two major branches: the innate immune system, which provides rapid but non-specific defense, and the adaptive immune system, which offers slower but highly targeted and long-lasting protection. Both systems undergo functional changes with age, but evidence indicates that these changes are not uniform across sexes.

According to the review, females generally maintain stronger adaptive immune responses throughout life compared to males. This heightened immune activity is partly attributed to genetic and hormonal differences. The X chromosome contains numerous immune-related genes, some of which may become more active with age due to incomplete X inactivation. In contrast, the Y chromosome carries fewer immune-related genes, contributing to sex-based differences in immune system regulation.

Sex hormones also play a key role. Estrogens can either enhance or suppress immune activity depending on their levels, while androgens such as testosterone tend to suppress immune responses overall. These hormonal effects help shape how immune function evolves over time in both sexes.

While females typically mount stronger immune responses and have greater resistance to infections, this heightened activity is also associated with a higher risk of autoimmune conditions later in life. Males, on the other hand, tend to show weaker adaptive immune responses with age and rely more heavily on innate immunity, which may contribute to poorer outcomes following infections and vaccinations.

These differences contribute to what researchers describe as the “morbidity–mortality paradox,” in which females tend to live longer than males but experience more years of chronic illness and disability.

The authors of the review note that understanding sex-based differences in immune aging is increasingly important for biomedical research and clinical care. Recognizing biological sex as a key variable may help improve treatment strategies and lead to more personalized approaches to preventing and managing age-related disease.