Aging activates escape of the silent X chromosome in the female mouse hippocampus.

ABSTRACT: Women live longer than men and exhibit less cognitive aging. The X chromosome contributes to sex differences, as females harbor an inactive X (Xi) and active X (Xa), in contrast to males with only an Xa. Thus, reactivation of silent Xi genes may contribute to sex differences. We use allele-specific, single-nucleus RNA sequencing to show that aging remodels transcription of the Xi and Xa across hippocampal cell types. Aging preferentially changed gene expression on the X's relative to autosomes. Select genes on the Xi underwent activation, with new escape across cells including in the dentate gyrus, critical to learning and memory. Expression of the Xi escapee Plp1, a myelin component, was increased in the aging hippocampus of female mice and parahippocampus of women. AAV-mediated

SUBMITTER: Gadek M 

PROVIDER: S-EPMC11881916 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature