This review examines the heterogeneity of senescent cells in the aging and diseased brain, covering differences in senescence induction, cell-cycle arrest mechanisms, cell-type biology, and microenvironments across CNS cell types.
Senescence in the brain is not a single, static fate but a dynamic, context-dependent trajectory shaped by cell type and environment; single-cell transcriptomics and spatial omics are reframing how these diverse programs are identified and studied.
As a narrative review, it does not report original experimental data or effect sizes. Findings are synthesized from heterogeneous studies, and causal relationships between senescent cell subtypes and disease outcomes remain largely unestablished in humans.
Therapeutic targeting of senescent brain cells (senolytics/senomorphics) should account for cell-type and microenvironment context, as a one-size-fits-all approach may miss or harm distinct senescent subpopulations. Multimodal molecular profiling combined with functional mouse studies is recommended before clinical translation.
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