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

Margaret Gadek, Cayce K Shaw, Samira Abdulai-Saiku, Rowan Saloner, Francesca Marino, Dan Wang, Luke W Bonham, Jennifer S Yokoyama, Barbara Panning, Bérénice A Benayoun, Kaitlin B Casaletto, Vijay Ramani, Dena B Dubal

Department of Neurology and Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.Department of Neurology and Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA. · pubmed

Paper

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

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Research summary

Aging activates the silent X chromosome in female mice, influencing gene expression in the hippocampus. The study explores the molecular changes associated with aging that may contribute to cognitive differences between sexes, addressing a potential mechanism underlying longevity and cognitive aging.

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