The Benayoun lab will explore why female mammals age differently than males. Sex differences in longevity are easy to see: Of the 34 humans currently living who are older than 110, 33 are women. But the molecular mechanisms that drive sex-based differences are less obvious. In preliminary studies, I found that immune cells isolated from aging mice show marked changes in the genes they activate—and that these differences are 10 to 20 times greater in females than in males. But are such variations driven by hormones alone—or do the sex chromosomes themselves (XX in females, XY in males) produce factors that independently influence this programming? Using methods in cell and molecular genetics, immunobiology, and bioinformatics, we will dissect the contributions made by hormones versus sex chromosomes by studying immune cells from a line of “sex reversed” mutant mice in which females have two X chromosomes but produce male levels of testosterone. My lab’s work will shed light on the sex-related susceptibilities to age-related immune changes and could lead to interventions that will extend healthy lifespan.