Aging impairs the function of immune cells and increases susceptibility to diseases such as anxiety and dementia. Nevertheless, some individuals exhibit resilience to age-related impairments, although the mechanisms are still unclear. This study investigated alterations in brain mononuclear cells and their association with age-related behavioral deficits in male and female rats. Flow cytometry was used to analyze the expression of CD45, CX3CR1, and CD163 on brain CD11b+ cells. Aging rats demonstrated reduced anxiety-like behavior, spatial learning, and social play, with certain sex differences. Young adult females showed hyperactivity and higher cognitive flexibility than same-aged males. Aging increased CD45 and CD163 expression within CD11b+ cells. Furthermore, sex-dependent correlations were observed between expression of CD163 and CX3CR1 within CD11b+ cells and locomotor activity in aging. Females might appear to be more susceptible to aging, suggesting microglial activation as a compensatory mechanism. These results suggest immune cell dynamics underlying sex-specific aging behavior.
© 2026. The Author(s).