Vascular Cell Senescence Contributes to Blood–Brain Barrier Breakdown
Open accessAbstract
Background and Purpose—: Age-related changes in the cerebrovasculature, including blood–brain barrier (BBB) disruption, are emerging as potential risks for diverse neurological conditions. Because the accumulation of senescent cells in tissues is increasingly recognized as a critical step leading to age-related organ dysfunction, we evaluated whether senescent vascular cells are associated with compromised BBB integrity. Methods—: Effects of vascular cell senescence on tight junction and barrier integrity were studied using an in vitro BBB model, composed of endothelial cells, pericytes, and astrocytes. In addition, tight junction coverage in microvessels and BBB integrity in BubR1 hypomorphic (BubR1 H/H ) mice, which display senescence cell-dependent phenotypes, were examined. Results—: When an in vitro BBB model was constructed with senescent endothelial cells and pericytes, tight junction structure and barrier integrity (evaluated by transendothelial electric resistance and tracer efflux assay using sodium fluorescein and Evans blue-albumin were significantly impaired. Endothelial cells and pericytes from BubR1 H/H mice had increased senescent-associated β-galactosidase activity and p16 INK4a expression, demonstrating an exacerbation of senescence. The coverage by tight junction proteins in the cortical microvessels were reduced in BubR1 H/H mice, consistent with a compromised BBB integrity from permeability assays. Importantly, the coverage of microvessels by end-feet of aquaporin 4–immunoreactive astrocytes was not altered in the cortex of the BubR1 H/H mice. Conclusions—: Our results indicate that accumulation of senescent vascular cells is associated with compromised BBB integrity, providing insights into the mechanism of BBB disruption related to biological aging.
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Accumulation of senescent endothelial cells is associated with impaired tight junction structure and compromised blood-brain barrier integrity.
“Accumulation of senescent endothelial cells is associated with impaired tight junction structure and compromised blood-brain barrier integrity [129] and it is linked to Sirt1 downregulation in senescent endothelial cells [130].”
From Ageing, Cellular Senescence and Neurodegenerative Disease (2018) · cites this paper as [129]
BUBR1 hypomorphic mice display blood-brain barrier leakage that correlates with premature senescence of neural endothelial cells and pericytes, which become SA β-gal positive and express p16.
“BUBR1 hypomorphic mice display leakage across the BBB that correlates with a propensity for neural endothelial cells and pericytes to prematurely senesce, become SA β-gal positive, and express p16 INK4A (66).”
From Cellular senescence in brain aging and neurodegenerative diseases: evidence and perspectives (2018) · cites this paper as [66]
Senescent endothelial cells may disrupt the integrity of the blood-brain barrier, an effect associated with age-related cognitive decline.
“Lastly, senescent endothelial cells may disrupt the integrity of the blood-brain barrier [1], an effect which has been associated with age-related cognitive decline [150].”
From DNA repair deficiency and senescence in concussed professional athletes involved in contact sports (2019) · cites this paper as [1]
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Astrocyte-endothelial interactions at the blood-brain barrier
Abbott, N. J., Rönnbäck, L., & Hansson, E. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1824 · Cited by 5,595 · see citing works
Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders
Baker, D. J., Wijshake, T., Tchkonia, T., LeBrasseur, N. K., Childs, B. G., van de Sluis, B., Kirkland, J. L., & van Deursen, J. M. (2011) · Nature · doi:10.1038/nature10600 · Cited by 3,670 · see citing works
Self-citationNeurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders
Zlokovic, B. V. (2011) · Nature Reviews Neuroscience · doi:10.1038/nrn3114 · Cited by 2,969 · see citing works
The role of senescent cells in ageing
van Deursen, J. M. (2014) · Nature · doi:10.1038/nature13193 · Cited by 2,623 · see citing works
Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors
Campisi, J. (2005) · Cell · doi:10.1016/j.cell.2005.02.003 · Cited by 2,359 · see citing works
The blood–brain barrier: an overview
Ballabh, P., Braun, A., & Nedergaard, M. (2004) · Neurobiology of Disease · doi:10.1016/j.nbd.2003.12.016 · Cited by 2,276 · see citing works
Blood-brain barrier breakdown in the aging human hippocampus
Montagne, A., Barnes, S. R., Sweeney, M. D., Halliday, M. R., Sagare, A. P., Zhao, Z., Toga, A. W., Jacobs, R. E., Liu, C. Y., Amezcua, L., et al. (2015) · Neuron · doi:10.1016/j.neuron.2014.12.032 · Cited by 2,102 · see citing works
Self-citationEndothelial/Pericyte Interactions
Armulik, A., Abramsson, A., & Betsholtz, C. (2005) · Circulation Research · doi:10.1161/01.res.0000182903.16652.d7 · Cited by 2,048 · see citing works
The essence of senescence: Figure 1.
Kuilman, T., Michaloglou, C., Mooi, W. J., & Peeper, D. S. (2010) · Genes & Development · doi:10.1101/gad.1971610 · Cited by 2,038 · see citing works
Four faces of cellular senescence
Rodier, F., & Campisi, J. (2011) · Journal of Cell Biology · doi:10.1083/jcb.201009094 · Cited by 2,016 · cited 1× · see citing works
“of senescent cells and (2) increased cyclin-dependent kinase inhibitors, p21 and p16, which are thought to mediate permanent cell cycle arrest.(18,19) Pulse treatment with H 2 O 2 is a commonly used method for stress-induced cell senescence.”
Cellular Senescence in Aging Primates
Herbig, U., Ferreira, M., Condel, L., Carey, D., & Sedivy, J. M. (2006) · Science · doi:10.1126/science.1122446 · Cited by 1,101 · see citing works
Endothelial Cell Senescence in Human Atherosclerosis: Role of Telomere in Endothelial Dysfunction
Minamino, T., Miyauchi, H., Yoshida, T., Ishida, Y., Yoshida, H., & Komuro, I. (2002) · Circulation · doi:10.1161/01.cir.0000013836.85741.17 · Cited by 1,061 · see citing works
Blood-brain barrier tight junction permeability and ischemic stroke
Sandoval, K. E., & WITT, K. A. (2008) · Neurobiology of Disease · doi:10.1016/j.nbd.2008.08.005 · Cited by 957 · see citing works
Blood–brain barrier: Ageing and microvascular disease – systematic review and meta-analysis
Farrall, A. J., & Wardlaw, J. M. (2009) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.07.015 · Cited by 882 · see citing works
BubR1 insufficiency causes early onset of aging-associated phenotypes and infertility in mice
Baker, D. J., Jeganathan, K. B., Cameron, J. D., Thompson, M., Juneja, S., Kopecka, A., Kumar, R., Jenkins, R. B., de Groen, P. C., Roche, P., et al. (2004) · Nature Genetics · doi:10.1038/ng1382 · Cited by 731 · see citing works
Self-citationBlood brain barrier: ageing and microvascular disease-systematic review and meta-analysis
Farrall, A., & Wardlaw, J. M. (2009) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2009.02.089 · Cited by 639 · see citing works
Matthews, C., Gorenne, I., Scott, S., Figg, N., Kirkpatrick, P., Ritchie, A., Goddard, M., & Bennett, M. (2006) · Circulation Research · doi:10.1161/01.res.0000233315.38086.bc · Cited by 615 · see citing works
Astrocyte Senescence as a Component of Alzheimer’s Disease
Bhat, R., Crowe, E. P., Bitto, A., Moh, M., Katsetos, C. D., Garcia, F. U., Johnson, F. B., Trojanowski, J. Q., Sell, C., & Torres, C. (2012) · PLoS ONE · doi:10.1371/journal.pone.0045069 · Cited by 586 · see citing works
Accumulation of senescent cells in Mitotic tissue of aging primates
Jeyapalan, J. C., Ferreira, M., Sedivy, J. M., & Herbig, U. (2007) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2006.11.008 · Cited by 571 · see citing works
Aging and Genome Maintenance: Lessons from the Mouse?
Hasty, P., Campisi, J., Hoeijmakers, J., van Steeg, H., & Vijg, J. (2003) · Science · doi:10.1126/science.1079161 · Cited by 553 · cited 1× · see citing works
“Impaired BBB Integrity and Reduced TJ Protein Coverage in BubR1H/H Mice Growing evidence suggests that lack of genomic integrity contributes to the aging process in both humans and mice.(23) Because BubR1 is an essential component of the spindle assembly checkpoint proteins during mitosis, BubR1 mice, in which BubR1 e…”
Brain Endothelial Cell-Cell Junctions: How to “Open” the Blood Brain Barrier
Stamatovic, S. M., Keep, R. F., & Andjelkovic, A. V. (2008) · Current Neuropharmacology · doi:10.2174/157015908785777210 · Cited by 516 · see citing works
SIRT1 in Neurodevelopment and Brain Senescence
Herskovits, A. Z., & Guarente, L. (2014) · Neuron · doi:10.1016/j.neuron.2014.01.028 · Cited by 493 · see citing works
Savidge, T., Newman, P., Pothoulakis, C., Rühl, A., Neunlist, M., Bourreille, A., Hurst, R. D., & Sofroniew, M. V. (2007) · Gastroenterology · doi:10.1053/j.gastro.2007.01.051 · Cited by 435 · see citing works
Reactive Astrocytes As Therapeutic Targets for CNS Disorders
Hamby, M. E., & Sofroniew, M. V. (2010) · Neurotherapeutics · doi:10.1016/j.nurt.2010.07.003 · Cited by 367 · see citing works
Nakagawa, S., Deli, M. A., Nakao, S., Honda, M., Hayashi, K., Nakaoke, R., Kataoka, Y., & Niwa, M. (2007) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-007-9195-4 · Cited by 364 · see citing works
Attenuating astrocyte activation accelerates plaque pathogenesis in APP/PS1 mice
Kraft, A. W., Hu, X., Yoon, H., Yan, P., Xiao, Q., Wang, Y., Gil, S. C., Brown, J., Wilhelmsson, U., Restivo, J. L., et al. (2013) · The FASEB Journal · doi:10.1096/fj.12-208660 · Cited by 324 · see citing works
Vascular endothelial dysfunction with aging: endothelin-1 and endothelial nitric oxide synthase
Donato, A. J., Gano, L. B., Eskurza, I., Silver, A., Gates, P. E., Jablonski, K., & Seals, D. R. (2009) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00689.2008 · Cited by 318 · see citing works
Phosphorylation of occludin correlates with occludin localization and function at the tight junction
Wong, V. (1997) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1997.273.6.c1859 · Cited by 288 · see citing works
Cellular senescence and the aging brain
Chinta, S. J., Woods, G., Rane, A., Demaria, M., Campisi, J., & Andersen, J. K. (2015) · Experimental Gerontology · doi:10.1016/j.exger.2014.09.018 · Cited by 282 · see citing works
Nishitsuji, K., Hosono, T., Nakamura, T., Bu, G., & Michikawa, M. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.225532 · Cited by 275 · see citing works
Self-citationBlood–brain-barriers in aging and in Alzheimer’s disease
Marques, F., Sousa, J. C., Sousa, N., & Palha, J. A. (2013) · Molecular Neurodegeneration · doi:10.1186/1750-1326-8-38 · Cited by 273 · see citing works
Microglia in the aging brain: relevance to neurodegeneration
Luo, X.-G., Ding, J.-Q., & Chen, S.-D. (2010) · Molecular Neurodegeneration · doi:10.1186/1750-1326-5-12 · Cited by 236 · see citing works
Ota, H., Eto, M., Kano, M. R., Ogawa, S., Iijima, K., Akishita, M., & Ouchi, Y. (2008) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.108.164368 · Cited by 227 · see citing works
Vascular smooth muscle cell senescence in atherosclerosis
GORENNE, I., KAVURMA, M., SCOTT, S., & BENNETT, M. (2006) · Cardiovascular Research · doi:10.1016/j.cardiores.2006.06.004 · Cited by 196 · see citing works
Effects of hypoxia on endothelial/pericytic co-culture model of the blood–brain barrier
Hayashi, K., Nakao, S., Nakaoke, R., Nakagawa, S., Kitagawa, N., & Niwa, M. (2004) · Regulatory Peptides · doi:10.1016/j.regpep.2004.05.023 · Cited by 163 · see citing works
Aging Enhances the Basal Production of IL-6 and CCL2 in Vascular Smooth Muscle Cells
Song, Y., Shen, H., Schenten, D., Shan, P., Lee, P. J., & Goldstein, D. R. (2011) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.111.236349 · Cited by 151 · see citing works
Regulation of blood-brain barrier endothelial cells by nitric oxide.
Janigro, D., West, G. A., Nguyen, T. S., & Winn, H. R. (1994) · Circulation Research · doi:10.1161/01.res.75.3.528 · Cited by 142 · see citing works
Calabria, A. R., Weidenfeller, C., Jones, A. R., de Vries, H. E., & Shusta, E. V. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.03793.x · Cited by 141 · see citing works
Sato, I., Morita, I., Kaji, K., Ikeda, M.-A., Nagao, M., & Murota, S. (1993) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1993.2153 · Cited by 128 · see citing works
A novel and simple method for culturing pericytes from mouse brain
Tigges, U., Welser-Alves, J. V., Boroujerdi, A., & Milner, R. (2012) · Microvascular Research · doi:10.1016/j.mvr.2012.03.008 · Cited by 110 · see citing works
McCaffrey, G., Willis, C. L., Staatz, W. D., Nametz, N., Quigley, C. A., Hom, S., Lochhead, J. J., & Davis, T. P. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06113.x · Cited by 93 · see citing works
Aging-Associated Vascular Phenotype in Mutant Mice With Low Levels of BubR1
Matsumoto, T., Baker, D. J., d’Uscio, L. V., Mozammel, G., Katusic, Z. S., & van Deursen, J. M. (2007) · Stroke · doi:10.1161/01.str.0000257967.86132.01 · Cited by 77 · see citing works
Self-citationPotential Involvement of LOX-1 in Functional Consequences of Endothelial Senescence
Khaidakov, M., Wang, X., & Mehta, J. L. (2011) · PLoS ONE · doi:10.1371/journal.pone.0020964 · Cited by 50 · see citing works
Contribution of endothelin-1 to disruption of blood-brain barrier permeability in dogs
Narushima, I., Kita, T., Kubo, K., Yonetani, Y., Momochi, C., Yoshikawa, I., Shimada, K., & Nakashima, T. (1999) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s002109900137 · Cited by 25 · see citing works
Effect of cellular senescence on the albumin permeability of blood-derived endothelial cells
Cheung, T. M., Ganatra, M. P., Peters, E. B., & Truskey, G. A. (2012) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00182.2012 · Cited by 22 · see citing works
Flagged first, then by citations
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The blood–brain barrier in systemic infection and inflammation
Galea, I. (2021) · Cellular and Molecular Immunology · doi:10.1038/s41423-021-00757-x · Cited by 762 · see citing works
Cellular senescence in brain aging and neurodegenerative diseases: evidence and perspectives
Baker, D. J., & Petersen, R. C. (2018) · Journal of Clinical Investigation · doi:10.1172/jci95145 · Cited by 514 · see citing works
Self-citationMechanisms and consequences of endothelial cell senescence
Bloom, S. I., Islam, M. T., Lesniewski, L. A., & Donato, A. J. (2022) · Nature Reviews Cardiology · doi:10.1038/s41569-022-00739-0 · Cited by 510 · see citing works
Endothelial cell senescence in aging-related vascular dysfunction
Jia, G., Aroor, A. R., Jia, C., & Sowers, J. R. (2019) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2018.08.008 · Cited by 454 · see citing works
Ageing, Cellular Senescence and Neurodegenerative Disease
Kritsilis, M., V. Rizou, S., Koutsoudaki, P. N., Evangelou, K., Gorgoulis, V. G., & Papadopoulos, D. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19102937 · Cited by 448 · see citing works
Inoue, Y., Shue, F., Bu, G., & Kanekiyo, T. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00640-5 · Cited by 356 · see citing works
Self-citationMechanisms of Vascular Aging, A Geroscience Perspective
Ungvari, Z. I., Tarantini, S., Sorond, F. A., Merkely, B. P., & Csiszár, A. (2020) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2019.11.061 · Cited by 329 · see citing works
Alkaline phosphatase: a novel treatment target for cardiovascular disease in CKD
Haarhaus, M. L., Brandenburg, V. M., Kalantar‐Zadeh, K., Stenvinkel, P., & Magnusson, P. (2017) · Nature Reviews Nephrology · doi:10.1038/nrneph.2017.60 · Cited by 316 · see citing works
Hallmarks of cardiovascular ageing
Abdellatif, M., Rainer, P. P., Sedej, S., & Kroemer, G. (2023) · Nature Reviews Cardiology · doi:10.1038/s41569-023-00881-3 · Cited by 284 · see citing works
Inflammation and premature aging in advanced chronic kidney disease
Kooman, J. P., Dekker, M. J. E., Usvyat, L. A., Kotanko, P., SANDE, F. M. V. D., Schalkwijk, C. G., Shiels, P. G., & Stenvinkel, P. (2017) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00256.2017 · Cited by 242 · see citing works
Cellular senescence at the crossroads of inflammation and Alzheimer's disease
Guerrero, A., De Strooper, B., & Arancibia-Cárcamo, I. L. (2021) · Trends in Neurosciences · doi:10.1016/j.tins.2021.06.007 · Cited by 236 · see citing works
Nuclear morphology is a deep learning biomarker of cellular senescence
Heckenbach, I., Mkrtchyan, G. V., Ezra, M. B., Bakula, D., Madsen, J. S., Nielsen, M. H., Oró, D., Osborne, B., Covarrubias, A. J., Idda, M. L., et al. (2022) · Nature Aging · doi:10.1038/s43587-022-00263-3 · Cited by 232 · see citing works
Kiss, T., Nyúl-Tóth, Á., Balasubramanian, P., Tarantini, S., Ahire, C., DelFavero, J., Yabluchanskiy, A., Csipo, T., Farkas, E., Wiley, G., et al. (2020) · GeroScience · doi:10.1007/s11357-020-00177-1 · Cited by 203 · see citing works
Yamazaki, Y., Shinohara, M., Shinohara, M., Yamazaki, A., Murray, M. E., Liesinger, A. M., Heckman, M. G., Lesser, E. R., Parisi, J. E., Petersen, R. C., et al. (2019) · Brain · doi:10.1093/brain/awz011 · Cited by 202 · see citing works
Self-citationCrespo-Garcia, S., Tsuruda, P. R., Dejda, A., Ryan, R. D., Fournier, F., Chaney, S. Y., Pilon, F., Dogan, T., Cagnone, G., Patel, P., et al. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2021.01.011 · Cited by 182 · see citing works
Astrocyte Senescence and Alzheimer’s Disease: A Review
Han, X., Zhang, T., Liu, H., Mi, Y., & Gou, X. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.00148 · Cited by 177 · see citing works
Age-related immune alterations and cerebrovascular inflammation
Finger, C. E., Moreno‐González, I., Gutiérrez, A., Moruno-Manchon, J. F., & McCullough, L. D. (2021) · Molecular Psychiatry · doi:10.1038/s41380-021-01361-1 · Cited by 177 · see citing works
Nrf2 deficiency in aged mice exacerbates cellular senescence promoting cerebrovascular inflammation
Fülöp, G., Kiss, T., Tarantini, S., Balasubramanian, P., Yabluchanskiy, A., Farkas, E., Bari, F., Ungvari, Z. I., & Csiszár, A. (2018) · GeroScience · doi:10.1007/s11357-018-0047-6 · Cited by 157 · see citing works
Stamatovic, S. M., Martínez-Revollar, G., Hu, A., Choi, J. H. K., Keep, R. F., & Andjelkovic, A. V. (2018) · Neurobiology of Disease · doi:10.1016/j.nbd.2018.09.006 · Cited by 149 · see citing works
Impact of pulse pressure on cerebrovascular events leading to age-related cognitive decline
Thorin‐Trescases, N., de Montgolfier, O., Pinçon, A., Raignault, A., Caland, L., Labbé, P., & Thorin, É. (2018) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00637.2017 · Cited by 151 · see citing works
Bermejo-Martín, J. F., Martín-Fernández, M., López-Mestanza, C., Duque, P., & Almansa, R. (2018) · Journal of Clinical Medicine · doi:10.3390/jcm7110400 · Cited by 141 · see citing works
Sun, J., Huang, Y., Gong, J., Wang, J., Fan, Y., Cai, J., Wang, Y., Qiu, Y., Wei, Y., Xiong, C., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-19042-y · Cited by 135 · see citing works
Neuroinflammation: The central enabler of postoperative cognitive dysfunction
Liu, Y., Yang, W., Xue, J., Chen, J., Liu, S., Zhang, S., Zhang, X., Gu, X., Dong, Y., & Qiu, P. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115582 · Cited by 136 · see citing works
Chen, Z.-A., Wu, C. ‐., Wu, S., Huang, C.-Y., Mou, C., Wei, K., Yen, Y., Chien, I.-T., Runa, S., Chen, Y., et al. (2024) · ACS Nano · doi:10.1021/acsnano.3c08993 · Cited by 128 · see citing works
Implicating endothelial cell senescence to dysfunction in the ageing and diseased brain
Graves, S. I., & Baker, D. J. (2020) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/bcpt.13403 · Cited by 118 · see citing works
Self-citationCellular senescence in aging and age-related diseases: Implications for neurodegenerative diseases
(2020) · International Review of Neurobiology · doi:10.1016/bs.irn.2020.03.019 · Cited by 114 · see citing works
Obesity-induced Cognitive Impairment in Older Adults: a Microvascular Perspective.
Balasubramanian, P., Kiss, T., Tarantini, S., Nyúl-Tóth, Á., Ahire, C., Yabluchanskiy, A., Csípő, T., Lipécz, Á., Tabák, Á., Institoris, A., et al. (2020) · American Journal of Physiology. Heart and Circulatory Physiology · doi:10.1152/ajpheart.00736.2020 · Cited by 106 · see citing works
Crespo‐Garcia, S., Fournier, F., Diaz-Marin, R., Klier, S. M., Ragusa, D., Masaki, L., Cagnone, G., Blot, G., Hafiane, I., Dejda, A., et al. (2024) · Nature Medicine · doi:10.1038/s41591-024-02802-4 · Cited by 108 · see citing works
The Blood–Brain Barrier and Its Intercellular Junctions in Age-Related Brain Disorders
Costea, L., Mészáros, Á., Bauer, H., Bauer, H., Traweger, A., Wilhelm, I., Farkas, A. E., & Krizbai, I. A. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20215472 · Cited by 98 · see citing works
Tarantini, S., Balasubramanian, P., DelFavero, J., Csípő, T., Yabluchanskiy, A., Kiss, T., Nyúl‐Tóth, Á., Mukli, P., Tóth, P., Ahire, C., et al. (2021) · GeroScience · doi:10.1007/s11357-021-00440-z · Cited by 100 · see citing works
Ahire, C., Nyúl‐Tóth, Á., DelFavero, J., Gulej, R., Faakye, J., Tarantini, S., Kiss, T., Kuan‐Celarier, A., Balasubramanian, P., Ungvari, A., et al. (2023) · Aging Cell · doi:10.1111/acel.13832 · Cited by 98 · see citing works
Blood-brain barrier disruption: a culprit of cognitive decline?
Che, J., Sun, Y., Deng, Y., & Zhang, J. (2024) · Fluids and Barriers of the CNS · doi:10.1186/s12987-024-00563-3 · Cited by 103 · see citing works
Jin, R., Xiao, A. Y., Chen, R., Granger, D. N., & Li, G. (2017) · Stroke · doi:10.1161/strokeaha.117.018839 · Cited by 95 · see citing works
Cellular senescence as a potential mediator of COVID‐19 severity in the elderly
Nehme, J., Borghesan, M., Mackedenski, S., Bird, T. G., & Demaria, M. (2020) · Aging Cell · doi:10.1111/acel.13237 · Cited by 94 · see citing works
Targeting cellular senescence in cancer and aging: roles of p53 and its isoforms
Beck, J. A., Turnquist, C., Horikawa, I., & Harris, C. C. (2020) · Carcinogenesis · doi:10.1093/carcin/bgaa071 · Cited by 94 · see citing works
Yamazaki, Y., Shinohara, M., Yamazaki, A., Ren, Y., Asmann, Y. W., Kanekiyo, T., & Bu, G. (2020) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.119.313169 · Cited by 89 · see citing works
Self-citationNyúl‐Tóth, Á., Patai, R., Csiszár, A., Ungvari, A., Gulej, R., Mukli, P., Yabluchanskiy, A., Benyó, Z., Sótonyi, P., Prodan, C. I., et al. (2024) · GeroScience · doi:10.1007/s11357-024-01194-0 · Cited by 91 · see citing works
Interactions between glial cells and the blood-brain barrier and their role in Alzheimer's disease.
Zhao, M., Jiang, X., Zhang, H., Sun, J.-H., Pei, H., Ma, L., Cao, Y., & Li, H. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101483 · Cited by 71 · see citing works
Preininger, M. K., & Kaufer, D. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23116217 · Cited by 84 · see citing works
Li, Q., Niu, X., Yi, Y., Chen, Y., Ji, Y., Zhang, J., Li, H., Xia, Y., Wang, Y., & Deng, Z. (2022) · ACS Nano · doi:10.1021/acsnano.2c10824 · Cited by 84 · see citing works
Senescent endothelial cells: Potential modulators of immunosenescence and ageing
Pantsulaia, I., Ciszewski, W. M., & Niewiarowska, J. (2016) · Ageing Research Reviews · doi:10.1016/j.arr.2016.05.011 · Cited by 80 · see citing works
Ximerakis, M., Holton, K. M., Giadone, R. M., Ozek, C., Saxena, M., Santiago, S., Adiconis, X., Dionne, D. A., Nguyễn, L., Shah, K. M., et al. (2023) · Nature Aging · doi:10.1038/s43587-023-00373-6 · Cited by 82 · see citing works
Cerebrovascular Senescence Is Associated With Tau Pathology in Alzheimer's Disease
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
Re-thinking the Etiological Framework of Neurodegeneration
Castillo, X., Castro‐Obregón, S., Gutiérrez-Becker, B., Gutiérrez‐Ospina, G., Karalis, N., Khalil, A. A., López‐Noguerola, J. S., Rodríguez, L. L., Martínez‐Martínez, E., Perez‐Cruz, C., et al. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00728 · Cited by 80 · see citing works
Aging, Cellular Senescence, and Progressive Multiple Sclerosis
Papadopoulos, D., Magliozzi, R., Mitsikostas, D. D., Gorgoulis, V. G., & Nicholas, R. S. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.00178 · Cited by 83 · see citing works
Nyúl‐Tóth, Á., Tarantini, S., DelFavero, J., Yan, F., Balasubramanian, P., Yabluchanskiy, A., Ahire, C., Kiss, T., Csípő, T., Lipécz, Á., et al. (2021) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00709.2020 · Cited by 76 · see citing works
Cellular senescence in the aging brain: A promising target for neurodegenerative diseases
Sahu, M. R., Rani, L., Subba, R., & Mondal, A. C. (2022) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2022.111675 · Cited by 75 · see citing works
Age-Related Hearing Loss: The Link between Inflammaging, Immunosenescence, and Gut Dysbiosis
Kociszewska, D., & Vlajkovic, S. M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23137348 · Cited by 77 · see citing works
Vascular ApoE4 impairs behavior by modulating gliovascular function
Yamazaki, Y., Liu, C.-C., Yamazaki, A., Shue, F., Martens, Y. A., Chen, Y., Qiao, W., Kurti, A., Oue, H., Ren, Y., et al. (2021) · Neuron · doi:10.1016/j.neuron.2020.11.019 · Cited by 71 · see citing works
Self-citationGulej, R., Nyúl‐Tóth, Á., Ahire, C., DelFavero, J., Balasubramanian, P., Kiss, T., Tarantini, S., Benyó, Z., Pacher, P., Csík, B., et al. (2023) · GeroScience · doi:10.1007/s11357-023-00870-x · Cited by 73 · see citing works
Cellular senescence in brain aging and cognitive decline
Shafqat, A., Khan, S., Omer, M. H., Niaz, M., Albalkhi, I., AlKattan, K. M., Yaqinuddin, A., Tchkonia, T., Kirkland, J. L., & Hashmi, S. K. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2023.1281581 · Cited by 75 · see citing works
Kiss, T., Nyúl-Tóth, Á., DelFavero, J., Balasubramanian, P., Tarantini, S., Faakye, J., Gulej, R., Ahire, C., Ungvari, A., Yabluchanskiy, A., et al. (2022) · GeroScience · doi:10.1007/s11357-022-00521-7 · Cited by 66 · see citing works
Effect of peripheral cellular senescence on brain aging and cognitive decline
Budamagunta, V., Kumar, A., Rani, A., Bean, L. A., Manohar‐Sindhu, S., Yang, Y., Zhou, D., & Foster, T. C. (2023) · Aging Cell · doi:10.1111/acel.13817 · Cited by 65 · see citing works
CDKN2A/p16INK4a expression is associated with vascular progeria in chronic kidney disease
Stenvinkel, P., Luttropp, K., McGuinness, D., Witasp, A., Qureshi, A. R., Wernerson, A. M., Nordfors, L., Schalling, M., Ripsweden, J., Wennberg, L. M., et al. (2017) · Aging · doi:10.18632/aging.101173 · Cited by 63 · see citing works
Andjelkovic, A. V., Stamatovic, S. M., Phillips, C. M., Martínez-Revollar, G., & Keep, R. F. (2020) · Fluids and Barriers of the CNS · doi:10.1186/s12987-020-00202-7 · Cited by 63 · see citing works
Pathomechanisms of Blood-Brain Barrier Disruption in ALS
Kakaroubas, N., Brennan, S. E., Keon, M., & Saksena, N. (2019) · Neuroscience Journal · doi:10.1155/2019/2537698 · Cited by 61 · see citing works
Repurposing metformin to treat age-related neurodegenerative disorders and ischemic stroke
Sharma, S., Nozohouri, S., Vaidya, B., & Abbruscato, T. J. (2021) · Life Sciences · doi:10.1016/j.lfs.2021.119343 · Cited by 60 · see citing works
Allen, B. D., & Limoli, C. L. (2021) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2021.12.002 · Cited by 60 · see citing works
Guo, L., Lin, F., Dai, H., Du, X., Yu, M., Zhang, J., Huang, H., Ge, W., Tao, G., & Pan, L. (2020) · Medical Science Monitor · doi:10.12659/msm.919293 · Cited by 56 · see citing works
Huang, J. A., Ding, J., Wang, X., Gu, C., He, Y., Li, Y., Fan, H., Xie, Q., Qi, X., Wang, Z., et al. (2022) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2022.09.002 · Cited by 56 · see citing works
van Hameren, G., Aboghazleh, R., Parker, E., Dreier, J. P., Kaufer, D., & Friedman, A. (2024) · Nature Reviews Neurology · doi:10.1038/s41582-024-00973-9 · Cited by 60 · see citing works
Endothelial Cell Senescence Effect on the Blood-Brain Barrier in Stroke and Cognitive Impairment
Real, M. G. C., Falcione, S. R., Boghozian, R., Clarke, M., Todoran, R., Pierre, A. S., Zhang, Y., Joy, T., & Jickling, G. C. (2024) · Neurology · doi:10.1212/wnl.0000000000210063 · Cited by 56 · see citing works
Role of pattern recognition receptors of the neurovascular unit in inflamm-aging
Wilhelm, I., Nyúl-Tóth, Á., Kozma, M., Farkas, A. E., & Krizbai, I. A. (2017) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00106.2017 · Cited by 56 · see citing works
Gong, S., Cao, G., Li, F., Chen, Z., Pan, X., Ma, H., Zhang, Y., Bo-yang, Y., & Kou, J. (2021) · Stroke · doi:10.1161/strokeaha.120.031410 · Cited by 55 · see citing works
Sah, E., Krishnamurthy, S., Ahmidouch, M. Y., Gillispie, G. J., Milligan, C., & Orr, M. E. (2021) · Life · doi:10.3390/life11030229 · Cited by 54 · see citing works
Acute ischemic stroke triggers a cellular senescence-associated secretory phenotype
Torres-Querol, C., Torres, P., Vidal, N., Portero‐Otín, M., Arqué, G., & Purroy, F. F. (2021) · Scientific Reports · doi:10.1038/s41598-021-95344-5 · Cited by 55 · see citing works
The cerebral endothelial cell as a key regulator of inflammatory processes in sterile inflammation
Ludewig, P., Winneberger, J., & Magnus, T. U. (2018) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2018.10.012 · Cited by 55 · see citing works
Tyrrell, D. J., Blin, M. G., Song, J., Wood, S. C., & Goldstein, D. R. (2020) · Journal of the American Heart Association · doi:10.1161/jaha.120.017820 · Cited by 53 · see citing works
Zhong, J., Yu, R., Zhou, Q., Liu, P., Liu, Z., & Bian, Y. (2021) · Food & Function · doi:10.1039/d1fo00155h · Cited by 51 · see citing works
Ikonomović, M. D., Mi, Z., & Abrahamson, E. E. (2016) · Ageing Research Reviews · doi:10.1016/j.arr.2016.11.003 · Cited by 52 · see citing works
Chen, Y., Joo, J. D., Chu, J. M. T., Chang, R. C., & Wong, G. T. C. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02905-8 · Cited by 49 · see citing works
The Post-amyloid Era in Alzheimer's Disease: Trust Your Gut Feeling
Osorio, C. P., Kanukuntla, T., Diaz, E. L., Jafri, N., Cummings, M., & Sfera, A. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00143 · Cited by 49 · see citing works
The role of the complement system in Multiple Sclerosis: A review
Saez-Calveras, N., & Stüve, O. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.970486 · Cited by 49 · see citing works
Rojas-Vázquez, S., Lozano‐Torres, B., García‐Fernández, A., Galiana, I., Pérez‐Villalba, A., Martí‐Rodrigo, P., Palop, M. J., Domínguez, M., Orzáez, M., Sancenón, F., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-44903-1 · Cited by 48 · see citing works
Liu, P., Bian, Y., Fan, Y., Zhong, J., & Liu, Z. (2019) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.9b06347 · Cited by 48 · see citing works
DNA repair deficiency and senescence in concussed professional athletes involved in contact sports
Schwab, N., Grenier, K., & Hazrati, L.-N. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-019-0822-3 · Cited by 47 · see citing works
Hampel, H. J., Lista, S., Néri, C., & Vergallo, A. (2019) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2019.101662 · Cited by 46 · see citing works
Aging, Senescence, and Dementia
Behfar, Q., Zuniga, A. R., & Adami, P. V. M. (2022) · The Journal of Prevention of Alzheimer s Disease · doi:10.14283/jpad.2022.42 · Cited by 49 · see citing works
VEGF receptor‐1 modulates amyloid β 1–42 oligomer‐induced senescence in brain endothelial cells
Angom, R. S., Wang, Y., Wang, E., Pal, K., Bhattacharya, S., Watzlawik, J. O., Rosenberry, T. L., Das, P., & Mukhopadhyay, D. (2018) · The FASEB Journal · doi:10.1096/fj.201802003r · Cited by 48 · see citing works
Roles and Mechanisms of DNA Methylation in Vascular Aging and Related Diseases
Xu, H., Li, S., & Liu, Y. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.699374 · Cited by 47 · see citing works
Csík, B., Nyúl‐Tóth, Á., Gulej, R., Patai, R., Kiss, T., DelFavero, J., Nagaraja, R. Y., Balasubramanian, P., Shanmugarama, S., Ungvari, A., et al. (2025) · Aging Cell · doi:10.1111/acel.70048 · Cited by 44 · see citing works
Targeting senescence to delay progression of multiple sclerosis
Oost, W., Talma, N., Meilof, J., & Laman, J. (2018) · Journal of molecular medicine · doi:10.1007/s00109-018-1686-x · Cited by 42 · see citing works
Dysfunction of the Blood-brain Barrier in Cerebral Microbleeds: from Bedside to Bench
Wang, H., Zhang, C., Qiu, Y., Chen, A., Li, Y., & Hu, B. (2021) · Aging and Disease · doi:10.14336/ad.2021.0514 · Cited by 47 · see citing works
The blood-brain barrier, a key bridge to treat neurodegenerative diseases
Hang, Z., Zhou, L., Xing, C., Wen, Y., & Du, H. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.102070 · Cited by 45 · see citing works
The need to incorporate aged animals into the preclinical modeling of neurological conditions
Sun, M., McDonald, S. J., Brady, R. D., Collins‐Praino, L. E., Yamakawa, G. R., Monif, M., O'Brien, T. J., CLOUD, G. C., Sobey, C. G., Mychasiuk, R., et al. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.12.027 · Cited by 43 · see citing works
Marino, J., Wigdahl, B. L., & Nonnemacher, M. R. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.00168 · Cited by 43 · see citing works
Liu, Y., Wang, L., Du, N., Yin, X., Shao, H., & Lin, Y. (2021) · Inflammation · doi:10.1007/s10753-021-01451-w · Cited by 43 · see citing works
Cellular senescence and the blood–brain barrier: Implications for aging and age-related diseases
Knopp, R. C., Erickson, M. A., Rhea, E. M., Reed, M. J., & Banks, W. A. (2023) · Experimental Biology and Medicine · doi:10.1177/15353702231157917 · Cited by 44 · see citing works
Historical and current perspectives on blood endothelial cell heterogeneity in the brain
Matsuoka, R. L., Buck, L. D., Vajrala, K. P., Quick, R. E., & Card, O. A. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-022-04403-1 · Cited by 39 · see citing works
Age-Related Midbrain Inflammation and Senescence in Parkinson’s Disease
Russo, T., & Rießland, M. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.917797 · Cited by 39 · see citing works
Ramadhiani, R., Ikeda, K., Miyagawa, K., Ryanto, G. R. T., Tamada, N., Suzuki, Y., Kirita, Y., Matoba, S., Hirata, K., & Emoto, N. (2023) · iScience · doi:10.1016/j.isci.2023.106662 · Cited by 37 · see citing works
Alzheimer’s Disease: From Pathogenesis to Mesenchymal Stem Cell Therapy – Bridging the Missing Link
Hu, J., & Wang, X. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.811852 · Cited by 40 · see citing works
Ting, K. K., Coleman, P. R., Zhao, Y., Vadas, M. A., & Gamble, J. R. (2021) · Vascular Biology · doi:10.1530/vb-20-0013 · Cited by 36 · see citing works
Deciphering therapeutic options for neurodegenerative diseases: insights from SIRT1
Wang, R., Wu, Y., Liu, R., Liu, M., Li, Q., Ba, Y., & Huang, H. (2022) · Journal of Molecular Medicine · doi:10.1007/s00109-022-02187-2 · Cited by 37 · see citing works
Wang, D., Kang, K., Sun, J., Lin, Q. D., Lv, Q., & Hai, J. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/4139330 · Cited by 36 · see citing works
Luo, N., Zhu, W., Li, X., Fu, M., Zhang, Y., Yang, F., Zhang, Y., Chen, Z., Zhang, Q., Peng, B., et al. (2024) · Neuro-Oncology · doi:10.1093/neuonc/noae153 · Cited by 37 · see citing works
Patai, R., Csík, B., Nyúl‐Tóth, Á., Gulej, R., Kordestan, K. V., Chandragiri, S. S., Shanmugarama, S., Tarantini, S., Mukli, P., Ungvari, A., et al. (2025) · GeroScience · doi:10.1007/s11357-025-01569-x · Cited by 35 · see citing works
Ungvari, A., Gulej, R., Csík, B., Mukli, P., Negri, S., Tarantini, S., Yabluchanskiy, A., Benyó, Z., Csiszár, A., & Ungvari, Z. I. (2023) · Nutrients · doi:10.3390/nu15214662 · Cited by 34 · see citing works
Balasubramanian, P., Kiss, T., Gulej, R., Toth, A. N., Tarantini, S., Yabluchanskiy, A., Ungvari, Z. I., & Csiszár, A. (2024) · Nutrients · doi:10.3390/nu16070952 · Cited by 33 · see citing works
Targeting Infectious Agents as a Therapeutic Strategy in Alzheimer’s Disease
Fülöp, T., Munawara, U., Larbi, A., Desroches, M., Rodrigues, S., Catanzaro, M., Guidolin, A., Khalil, A., Bernier, F., Barron, A. E., et al. (2020) · CNS Drugs · doi:10.1007/s40263-020-00737-1 · Cited by 32 · see citing works
- Authors
- Yamazaki, Y., Baker, D. J., Tachibana, M., Liu, C.-C., van Deursen, J. M., Brott, T. G., Bu, G., & Kanekiyo, T.
- Affiliations
- Mayo Clinic (US)
- From the Departments of Neuroscience (Y.Y., M.T., C-C.L., G.B., T.K.) and Neurology (T.G.B.), Mayo Clinic, Jacksonville, FL; and Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN (D.J.B., J.M.v.D.).
- Venue
- Stroke
- Published
- 2016-04
- Volume
- 47
- Issue
- 4
- Pages
- 1068-1077
- ISSN
- 0039-2499 (ISSN-L)
- 1524-4628
- PMC
- PMC4811685
- OpenAlex
- W2273856223
- Cited by
- 263
- References
- 45
- Citations by year
- 2026: 30 · 2025: 33 · 2024: 30 · 2023: 35 · 2022: 33 · 2021: 30 · 2020: 31 · 2019: 15 · 2018: 12 · 2017: 9 · 2016: 3 · 2015: 1 · 2012: 1
- FWCI
- 7.12
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Stroke (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Funders
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
- National Institutes of Health
- National Institute on Aging (RF1AG051504, R01AG027924, RF1AG046205, R01AG046205, R01AG035355, P50AG016574)
- National Cancer Institute (R01CA096985)
- National Institute of Neurological Disorders and Stroke (P01NS074969)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- blood-brain barrier disruption, tight junctions, endothelial cells, pericytes, astrocytes, senescence-associated β-galactosidase, p16INK4a, blood-brain barrier permeability, aging, cerebral vasculature, aquaporin-4
- MeSH terms
- Aging, Animals, Astrocytes, beta-Galactosidase, Blood-Brain Barrier, Brain, Capillary Permeability, Cellular Senescence, Tight Junctions, Cyclin-Dependent Kinase Inhibitor p16, Pericytes, Endothelial Cells, Mice, Aquaporin 4
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