Uncovering the signatures of aging and senescence in the human dorsolateral prefrontal cortex.

ABSTRACT: We performed Visium spatial transcriptomics (ST) and single-nucleus RNA sequencing (snRNA-seq) on a cohort of nonpathological human tissues to uncover signatures of aging and senescence in the dorsolateral prefrontal cortex (dlPFC). In doing so, we identified gene expression changes characteristic of aged cortical layers. The cellular composition of the dlPFC also changed with age, with increased homeostatic astrocyte abundance and with decreased somatostatin (SST) inhibitory neurons. Nuclei from dlPFC cell types displayed a strong decline in oxidative phosphorylation- and cytoplasmic translation-related genes with age. Additionally, oligodendrocytes showed several hallmarks of senescence and a linear increase in CDKN2A expression with age. Combined analysis of ST and snRNA-seq datasets re

SUBMITTER: Sloan NX 

PROVIDER: S-EPMC12903411 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature