X CHROMOSOME-DERIVED MECHANISMS OF SEX DIFFERENCES IN LIFESPAN AND BRAIN AGING

Abstract Women live longer than men worldwide – and also show cognitive resilience in many aging populations. One major source of biologic difference between the sexes is that females have two X chromosomes males one. This sex chromosome complement causes unique X-derived mechanisms are sex-specific. In mammalian development, one randomly inactivates XX cells. mosaics with active each cell being either maternally-derived (Xm) or paternally-derived (Xp), whereas harbor only a all Interestingly, some considerable complete skew toward Xm Xp. We utilized several genetic models biology to understand aging. found contributes longevity better cognition male female mice. aging, manipulation express (Xm), like males, accelerated decline epigenetic brain suggests harmful mosaicism (Xm+Xp) provides buffer deleterious processes To assess if alters transcription, we used mice nuclear localized reporters sorted from Xp neurons young hippocampi. imprinted genes within hippocampal neurons, suggesting silenced loci. Our data maternal accelerates deficits. Understanding how impairs function could increase understanding heterogeneity differences heath unlock new pathways against deficits females, both.