2026-06-16 カリフォルニア大学サンディエゴ校（UCSD）
Researchers found that three cell types enter a senescent state during development: vascular endothelial cells (red), brain-resident macrophages (green) and choroid plexus epithelial cells (yellow). Credit: Ella Maru Studio, conceptualized by Ashley Watson and Hiruy Meharena
＜関連情報＞
- https://today.ucsd.edu/story/researchers-offer-new-insights-on-cells-that-build-protective-brain-barriers
- https://www.cell.com/cell/fulltext/S0092-8674(26)00581-7
持続性および一過性の老化細胞は脳関門の発達に寄与する Persistent and transient senescent cells contribute to brain-barrier development
L. Ashley Watson ∙ Zoe Adelsheim ∙ Mackenzie J. Carter, ∙ … ∙ Rania H. Palaniappan ∙ John M. Augustine ∙ Hiruy S. Meharena
Cell Published:June 10, 2026
DOI:https://doi.org/10.1016/j.cell.2026.05.022
Highlights
- Distinct senescent states arise across brain-barrier cell lineages
- Endothelial cells and macrophages engage a transient inflammatory senescent state
- Choroid plexus epithelium maintains a persistent non-inflammatory senescent state
- Senescent cell ablation alters vascular patterning and CSF homeostasis
Summary
Establishment of the blood-brain barrier (BBB) and blood-cerebrospinal fluid (CSF) barrier requires precise coordination between diverse cell types to protect and nourish the brain. Here, we identify developmentally programmed p21+ senescent cells that exhibit divergent senescence-associated features across these two brain interfaces in mice. In the choroid plexus (ChP), epithelial cells adopt a lifelong, non-inflammatory senescent state associated with CSF production and blood-CSF barrier integrity. In contrast, vascular endothelial cells and brain-resident macrophages transiently exhibit pro-inflammatory senescence profiles during brain vascularization, with reciprocal signaling linked to angiogenic patterning and extracellular matrix assembly. The ablation of p21+ cells during mid-gestation disrupts brain vascular patterning and ChP integrity, which results in hemorrhage, impaired CSF production, and ventricular collapse. These findings indicate that embryonic senescent cells adopt divergent transient and long-lived states that support brain-barrier formation and homeostasis, thus reframing the prevailing view of persistent senescence beyond solely a pathological state.
