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Aging in mice alters regionally enriched striatal astrocytes

Linker, Kay E
Duran-Laforet, Violeta
Ollivier, Matthias
Yu, Xinzhu
Schafer, Dorothy P
Khakh, Baljit S
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Journal Article
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2025-09-26
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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.

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Linker KE, Duran-Laforet V, Ollivier M, Yu X, Schafer DP, Khakh BS. Aging in mice alters regionally enriched striatal astrocytes. Nat Commun. 2025 Sep 26;16(1):8496. doi: 10.1038/s41467-025-63429-8. PMID: 41006292; PMCID: PMC12475473.

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10.1038/s41467-025-63429-8
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41006292
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Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/ licenses/by/4.0/. © The Author(s) 2025