Abstract
Aging is the key risk factor for loss of cognitive function and neurodegeneration but our knowledge of molecular dynamics across the aging brain is very limited. Here we perform spatiotemporal RNA-seq of mouse brain aging, encompassing 847 samples from 15 regions spanning 7 ages. We identify a brain-wide gene signature representing aging in glia with spatially-defined magnitudes. By integrating spatial and single-nuclei transcriptomics, we reveal that glia aging is profoundly accelerated in white matter compared to cortical areas. We further discover region-specific expression changes in specialized neuronal populations. Finally, we discover distinct clusters of brain regions that differentially express genes associated with 3 human neurodegenerative diseases, highlighting regional aging as a potential modulator of disease. Our findings identify molecular foci of brain aging, providing a foundation to target age-related cognitive decline.
One-Sentence Summary Cartography of gene expression changes across the central nervous system of mice identifies hotspots of accelerated brain aging.
Competing Interest Statement
The authors have declared no competing interest.