Blood-brain barrier dysfunction in aging is mediated by brain endothelial senescence

被引：5

作者：

Novo, Joao P. ^{[1
,2
,3
]}

Gee, Lucy ^{[4
]}

Caetano, Carolina A. ^{[1
,3
]}

Tome, Ines ^{[1
,3
]}

Vilaca, Andreia ^{[3
,5
]}

von Zglinicki, Thomas ^{[6
]}

Moreira, Irina S. ^{[1
,3
,7
]}

Jurk, Diana ^{[4
]}

Rosa, Susana ^{[1
,3
]}

Ferreira, Lino ^{[1
,3
,5
]}

机构：

[1] Univ Coimbra, CNC UC Ctr Neurosci & Cell Biol, Coimbra, Portugal

[2] Univ Coimbra, Inst Interdisciplinary Res, Doctoral Programme Expt Biol & Biomed PDBEB, Coimbra, Portugal

[3] Univ Coimbra, CIBB Ctr Innovat Biomed & Biotechnol, Coimbra, Portugal

[4] Mayo Clin, Dept Physiol & Biomed Engn, Rochester, MN 55905 USA

[5] Univ Coimbra, Fac Med, Coimbra, Portugal

[6] Newcastle Univ, Biosci Inst, Fac Med Sci, Newcastle Upon Tyne, England

[7] Univ Coimbra, Dept Life Sci, Coimbra, Portugal

来源：

AGING CELL | 2024年 / 23卷 / 09期

基金：

英国生物技术与生命科学研究理事会;

关键词：

aging; blood-brain barrier; brain endothelial cells; senescence; senolytics; PHENOTYPE; CELLS;

D O I：

10.1111/acel.14270

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

BBB dysfunction during aging is characterized by an increase in its permeability and phenotypic alterations of brain endothelial cells (BECs) including dysregulation of tight junction's expression. Here we have investigated the role of BEC senescence in the dysfunction of the BBB. Our results suggest that the transition from young to aged BBB is mediated, at least in part by BEC senescence. The current study shows that the accumulation of senescent brain endothelial cells (BECs) may mediate the transition from a young to an aged BBB. Aged BECs have a higher expression of senescent markers and impaired occludin expression which interferes with BBB function. These phenotypes were partially reverted after the systemic elimination of p16+ cells by genetic means. The study contributes for a better understanding of BBB dysfunction during aging.image

引用

页数：6

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