Year: 2025
Type: article
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: Nature Communications
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: U.S. Department of Health and Human Services, Alzheimer's Association, Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, BrightFocus Foundation, Massachusetts Life Sciences Center, Broad Institute, National Institutes of Health, National Institute on Aging, National Institute of Mental Health, National Institute on Drug Abuse, National Institute of Neurological Disorders and Stroke
Awards: G1398481423, G2071240082, Dissecting the impact of senescence on microglia function and neurodegeneration, G2230189501, Harnessing spatial transcriptomics to investigate the intersection of senescence and inflammation in neurodegeneration, G2861168203, Fundamental astrocyte biology in intact neural circuits, G3258152776, G3439387492, G4680456693, Dissecting the impact of senescence on microglia function and neurodegeneration, Molecular identity, cellular physiology, and in vivo functions of nucleus accumbens astrocytes, G748805838, A Spatial Transcriptomic Approach to Interrogate Vascular-Associated Microglia in AD, How Do Synaptic Connections Change in Demyelinating Disease?, G8349874750, G8395461312, New tools to target, identify and characterize astrocytes in the adult nervous system, G9000065589, G9000252321, Microglia-Astrocyte Crosstalk Regulating SynapseRemodeling
OpenAlex ID: W4414543290