Aging in mice alters regionally enriched striatal astrocytes

Kay E. Linker (), Violeta Duran-Laforet, Matthias Ollivier, Xinzhu Yu, Dorothy P. Schafer and Baljit S. Khakh ()
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Kay E. Linker: University of California, Los Angeles
Violeta Duran-Laforet: University of Massachusetts Chan Medical School
Matthias Ollivier: University of California, Los Angeles
Xinzhu Yu: University of California, Los Angeles
Dorothy P. Schafer: University of Massachusetts Chan Medical School
Baljit S. Khakh: University of California, Los Angeles

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: Abstract Aging affects multiple organs and within the brain drives distinct molecular changes across different cell types. The striatum encodes motor behaviors that decline with age, but our understanding of how cells within the striatum change remains incomplete. Using single-cell RNA sequencing from young and aged mice we identify molecularly distinct astrocyte subtypes. We show that astrocytes change significantly with age, exhibiting downregulation of genes, reduced diversity, and a shift to more homogenous inflammatory transcriptomic profiles. By exploring where striatal astrocyte subtypes are located with single-cell resolution, we map astrocytes enriched in dorsal, medial, and ventral striatum. Age increases inflammatory marker transcripts in dorsal striatal astrocytes, which display greater age-related changes than ventral striatal astrocytes. We impute molecular interactions between astrocytes and neurons and find that age particularly reduced interactions related to Nrxn2. Our data show that aging alters regionally enriched striatal astrocytes asymmetrically, with dorsal striatal astrocytes exhibiting greater age-related molecular changes.

Date: 2025
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DOI: 10.1038/s41467-025-63429-8

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