Astrocyte-endothelial cell interaction in the aging brain
Increased angiotensin signaling from senescent astrocytes may degrade astrocyte-to-endothelial support for the blood-brain barrier during aging
2025-10-01
(Press-News.org)
Aging is the major risk factor for many central nervous system (CNS) pathological conditions and diseases, such as Alzheimer’s Disease and stroke. In the aging brain, a dysfunctional or “leaky” blood-brain barrier (BBB) is considered a key trigger for neurodegeneration.
Within the neurovascular unit, the functional BBB comprises cell-cell interactions between endothelium, astrocytes, pericytes, and the vascular basement membrane and matrix. Astrocytes lie in close contact with endothelial cells through their endfeet and participate in BBB maintenance and regulation. “There are significant gaps in the knowledge and the role of aging in inducing BBB dysfunction is unclear,” says Professor Eng H. Lo, who leads the research group that contributed towards a better understanding of this aspect.
Many in vivo and in vitro studies have shown that astrocytes change with aging, and an accumulation of reactive A1-type astrocytes has been reported for aging and Alzheimer’s Disease. The present study describes the effects of senescence on the ability of astrocytes to modulate brain endothelial cell permeability. The study was published online in the journal Neuroprotection on September 21, 2025. “The study demonstrated that young astrocytes increased the barrier function of brain endothelial cells in culture, whereas the senescent astrocytes did not,” says Prof. Lo, highlighting the key finding of their study.
To model aging in vitro, cell cultures in low and high cumulated population doublings (CPD) were used as young and aged senescent cells, respectively. In both the co-culture system and conditioned media transfer, BBB-supportive effects from donor astrocytes to receiver endothelial cells depended on the age of astrocytes. Senescent astrocytes lost their BBB-supporting effects on brain endothelial cells, including changes in BSA permeability and BBB-related protein expression. Further, angiotensinogen (AGT) was silenced by small interfering RNA (siRNA) in senescent astrocyte to test the effect of angiotensin signaling on endothelial permeability. Our study showed that these effects were mediated by an increase in expression of angiotensinogen (AGT) in senescent astrocytes. “Increased AGT in older astrocytes may play a role in the loss of endothelial barrier function in aging brain,” says Prof. Lo, describing the role of AGT in ageing-mediated BBB dysfunction.
These findings suggest that the cell-cell interaction in the neurovascular unit changes with aging, leading to the dysfunction of the BBB. “The study demonstrates that upregulated angiotensin signaling in senescent astrocytes may partly contribute to a decrease in endothelial barrier function within the aging neurovascular unit,” concludes Prof. Lo. Since there is a strong literature on the pharmacology of the angiotensin pathway, future studies should investigate whether therapeutic approaches can be developed to modulate this signal to rescue BBB function in the aging brain.
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Reference
DOI: 10.1002/nep3.70013
About Harvard Medical School
Harvard Medical School, a world-renowned institution founded in 1782, is dedicated to excellence in medical education, research, and clinical care. It is a graduate school of Harvard University and a leader in advancing biomedical science, training physicians, and improving human health through its affiliated hospitals.
Website: https://hms.harvard.edu/
About Eng H. Lo from Massachusetts General Hospital and Harvard Medical School
Eng H. Lo, Ph.D., is a renowned neuroscientist and Professor at Harvard Medical School. He leads the Neuroprotection Research Laboratory at Massachusetts General Hospital, focusing on the mechanisms of ischemic stroke and brain repair. His pioneering work on the neurovascular unit and blood-brain barrier has significantly advanced the understanding of cerebrovascular diseases, driving the development of novel therapeutic strategies.
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[Press-News.org] Astrocyte-endothelial cell interaction in the aging brain
Increased angiotensin signaling from senescent astrocytes may degrade astrocyte-to-endothelial support for the blood-brain barrier during aging
