Astrocyte-enriched pan-brain aging transcriptome

Normal brain aging is marked by a cognitive decline, spurred by changes in cellular metabolism and homeostatic dysregulation, as well as modifications in synapses and neuronal connectivity. Astrocytes are well positioned as an effector of these changes, although how properties of astrocytes change with age remains unclear. Here, we address this question by profiling astrocytic gene expression from multiple brain regions of adult (4 month-old) and aged (2 years-old) mice. We isolated mRNA from transgenic mice where ribosomes within astrocytes were genetically tagged (GFAP-cre x RPL22-HA, astrocyte ribotag). We then used RNA sequencing to identify and quantify the astrocyte-enriched mRNA, analyzing 4 different brain regions: visual cortex, somatomotor cortex, hypothalamus, and cerebellum. Overall, we find that astrocyte expression of inflammatory and immune response factors increase with age, as well as changes in genes associated with metabolism, cholesterol synthesis, and synaptogenesis. Going forward, these data contribute to an understanding of astrocyte diversity and provide insight into the role of astrocytes in normal aging.