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Aging in mice alters regionally enriched striatal astrocytes

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  • Kay E. Linker

    (University of California, Los Angeles
    University of California, Los Angeles
    RefinedScience)

  • Violeta Duran-Laforet

    (University of Massachusetts Chan Medical School)

  • Matthias Ollivier

    (University of California, Los Angeles)

  • Xinzhu Yu

    (University of California, Los Angeles
    University of Texas Health Science Center at Houston)

  • Dorothy P. Schafer

    (University of Massachusetts Chan Medical School)

  • Baljit S. Khakh

    (University of California, Los Angeles
    University of California, Los Angeles)

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.

Suggested Citation

  • Kay E. Linker & Violeta Duran-Laforet & Matthias Ollivier & Xinzhu Yu & Dorothy P. Schafer & Baljit S. Khakh, 2025. "Aging in mice alters regionally enriched striatal astrocytes," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63429-8
    DOI: 10.1038/s41467-025-63429-8
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