The Aging Astrocyte Transcriptome from Multiple Regions of the Mouse Brain

TLDR

Aging brains exhibit cognitive decline linked to reduced synapse number, altered metabolism, and uncertain changes in astrocyte‑mediated synapse regulation. The study generated and compared aged versus adult astrocyte transcriptomes from multiple brain regions, identifying region‑specific aging changes and heterogeneous synapse‑regulating gene expression. The RNA‑seq resource shows that aging astrocytes largely maintain homeostatic genes but upregulate synapse‑eliminating and reactive‑like genes, creating a permissive environment for synapse loss and neuronal damage that may underlie cognitive decline.

Abstract

Aging brains undergo cognitive decline, associated with decreased neuronal synapse number and function and altered metabolism. Astrocytes regulate neuronal synapse formation and function in development and adulthood, but whether these properties change during aging, contributing to neuronal dysfunction, is unknown. We addressed this by generating aged and adult astrocyte transcriptomes from multiple mouse brain regions. These data provide a comprehensive RNA-seq database of adult and aged astrocyte gene expression, available online as a resource. We identify astrocyte genes altered by aging across brain regions and regionally unique aging changes. Aging astrocytes show minimal alteration of homeostatic and neurotransmission-regulating genes. However, aging astrocytes upregulate genes that eliminate synapses and partially resemble reactive astrocytes. We further identified heterogeneous expression of synapse-regulating genes between astrocytes from different cortical regions. We find that alterations to astrocytes in aging create an environment permissive to synapse elimination and neuronal damage, potentially contributing to aging-associated cognitive decline.