Aging in mice alters regionally enriched striatal astrocytes
Linker, Kay E ; Duran-Laforet, Violeta ; Ollivier, Matthias ; Yu, Xinzhu ; Schafer, Dorothy P ; Khakh, Baljit S
Student Authors
Faculty Advisor
Academic Program
UMass Chan Affiliations
Document Type
Publication Date
Keywords
Subject Area
Collections
Files
Embargo Expiration Date
Link to Full Text
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.
Source
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.