A researcher's guide to studying sex differences in immune aging.

Sex differences in immune system aging significantly impact disease susceptibility and vaccine responses among older adults, but with notable disparities between men and women. This area has gained importance because vaccines can exhibit differential efficacy by sex in aging populations, underscoring the need for sex-specific strategies. As the global population ages, understanding these sex-based immune differences is crucial for developing targeted interventions for age-related diseases. Addressing these disparities requires robust preclinical models that mimic human immune aging to uncover mechanisms and inform personalized approaches. In this review we assess the translational potential of preclinical mouse models in studying sex differences in immune aging, and emphasize the urgency of sex-specific interventions to improve health outcomes in older adults.