How age and sex interaction is associated with immune aging with implications for vaccines and age-related autoimmunity.

Immunosenescence is not a uniform decline but a trajectory shaped jointly by age and sex. Using continuous high-dimensional immunophenotyping, we show that aging T cells accumulate a senescent signature of CD28 loss and CD57 gain, and that males reach an inverted CD4:CD8 ratio earlier and more severely than females. We argue that age-by-sex stratification should guide vaccination and geroprotective strategies in an aging population.