Implicating endothelial cell senescence to dysfunction in the ageing and diseased brain
Open accessAbstract
Cerebrovascular endothelial cells (CECs) are integral components of both the blood‐brain barrier (BBB) and the neurovascular unit (NVU). As the primary cell type of the BBB, CECs are responsible for the tight regulation of molecular transport between the brain parenchyma and the periphery. Additionally, CECs are essential in neurovascular coupling where they help regulate cerebral blood flow in response to regional increases in cellular demand in the NVU. CEC dysfunction occurs during both normative ageing and in cerebrovascular disease, which leads to increased BBB permeability and neurovascular uncoupling. This MiniReview compiles what is known about the molecular changes underlying CEC dysfunction, many of which are reminiscent of cells that have become senescent. In general, cellular senescence is defined as an irreversible growth arrest characterized by the acquisition of a pro‐inflammatory secretory phenotype in response to DNA damage or other cellular stresses. We discuss evidence for endothelial cell senescence in ageing and cardiovascular disease, and how CEC senescence may contribute to age‐related cerebrovascular dysfunction.
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The expression of senescent factors, SASPs in particular, creates an inflammatory milieu within the brain believed to modulate neuroimmune processes while also compromising the integrity of the BBB.
“The expression of senescent factors, SASPs in particular, creates an inflammatory milieu within the brain believed to modulate neuroimmune processes while also compromising the integrity of the BBB (169, 170).”
From Connecting aging biology and inflammation in the omics era (2022) · cites this paper as [169]
The endothelial cells that line the blood vessels in the brain become less effective with age, and an increase in their permeability can lead to a compromised barrier.
“The endothelial cells that line the blood vessels in the brain become less effective with age. An increase in the permeability of these cells can lead to a compromised barrier.149”
From Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances (2025) · cites this paper as [149]
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Nag, S., Manias, J. L., Eubanks, J. H., & Stewart, D. J. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20071594 · Cited by 25 · see citing works
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Han, Y., & Kim, S. Y. (2023) · Experimental & Molecular Medicine · doi:10.1038/s12276-022-00906-w · Cited by 201 · see citing works
Connecting aging biology and inflammation in the omics era
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Jiang, Q., Liu, J., Huang, S., Wang, X.-Y., Chen, X., Liu, G.-H., Ye, K., Song, W., Masters, C. L., Wang, J., et al. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02145-7 · Cited by 165 · see citing works
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Bryant, A. G., Hu, M., Carlyle, B. C., Arnold, S. E., Frosch, M. P., Das, S., Hyman, B. T., & Bennett, R. E. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.575953 · Cited by 79 · see citing works
Vascular Senescence: A Potential Bridge Between Physiological Aging and Neurogenic Decline
Rojas-Vázquez, S., Blasco-Chamarro, L., López-Fabuel, I., Martínez-Máñez, R., & Fariñas, I. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.666881 · Cited by 15 · see citing works
- Authors
- Graves, S. I., & Baker, D. J.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Baker, Darren J.
- ORCID
- Baker, Darren J.
- Venue
- Basic & Clinical Pharmacology & Toxicology
- Publisher
- Wiley
- Published
- 2020-03-23
- Volume
- 127
- Issue
- 2
- Pages
- 102-110
- ISSN
- 1742-7835 (ISSN-L)
- 1742-7843
- PMC
- PMC7384943
- OpenAlex
- W3012161629
- Cited by
- 118
- References
- 85
- Citations by year
- 2026: 21 · 2025: 21 · 2024: 23 · 2023: 17 · 2022: 17 · 2021: 12 · 2020: 5 · 2015: 1 · 2012: 1
- FWCI
- 1.27
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Basic & Clinical Pharmacology & Toxicology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Glenn Foundation for Medical Research
- Cure Alzheimer's Fund
- Ellison Medical Foundation
- National Institutes of Health (AG53229)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- endothelial cell senescence, brain endothelial cells, blood-brain barrier, neurovascular unit, neurovascular uncoupling, cerebral blood flow, brain aging, cerebrovascular disease, senescence-associated secretory phenotype, DNA damage, blood-brain barrier permeability
- MeSH terms
- Neurovascular Coupling, Aging, Blood-Brain Barrier, Brain, Capillary Permeability, Cerebrovascular Disorders, Humans, Nitric Oxide, Cytokines, Cellular Senescence, Endothelial Cells, Nitric Oxide Synthase Type III
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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