{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:59:19Z","timestamp":1791475159613,"version":"4.3.4"},"reference-count":84,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,3,23]],"date-time":"2020-03-23T00:00:00Z","timestamp":1584921600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100001642","name":"Glenn Foundation for Medical Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001642","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007625","name":"Cure Alzheimer's Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007625","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000863","name":"Ellison Medical Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000863","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AG53229"],"award-info":[{"award-number":["AG53229"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Basic Clin Pharma Tox"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cerebrovascular endothelial cells (CECs) are integral components of both the blood\u2010brain 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\u2010inflammatory 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\u2010related cerebrovascular dysfunction.<\/jats:p>","DOI":"10.1111\/bcpt.13403","type":"journal-article","created":{"date-parts":[[2020,3,12]],"date-time":"2020-03-12T06:35:41Z","timestamp":1583994941000},"page":"102-110","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":113,"title":["Implicating endothelial cell senescence to dysfunction in the ageing and diseased brain"],"prefix":"10.1111","volume":"127","author":[{"given":"Sara I.","family":"Graves","sequence":"first","affiliation":[{"name":"Departments of Biochemistry and Molecular Biology Mayo Clinic Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9006-1939","authenticated-orcid":false,"given":"Darren J.","family":"Baker","sequence":"additional","affiliation":[{"name":"Departments of Biochemistry and Molecular Biology Mayo Clinic Rochester Minnesota"},{"name":"Departments of Pediatric and Adolescent Medicine Mayo Clinic Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,3,23]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(16)30029-1"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2007.07.015"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11934"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.12.032"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0297-y"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awt188"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-161222"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dadm.2017.10.001"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhq224"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2018.08.008"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.306301"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-018-0030-z"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-121808-102144"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI95145"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4000"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI95146"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000269183.13937.e8"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00230.2009"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.306531"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M001644200"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.6409-11.2012"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2011.07542.x"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000260180.42709.29"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.115.010835"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12979-015-0029-9"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.109.570515"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2011.12.016"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/63.1.12"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2011.09.022"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2004.10.005"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2011.03.016"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.118.311400"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/gls242"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20071594"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2016.5974"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI9369"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0440-4"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2008.05.020"},{"issue":"4","key":"e_1_2_5_40_1","first-page":"560","article-title":"Elevated soluble vascular cell adhesion molecule\u20101 is associated with cerebrovascular resistance and cognitive function","volume":"72","author":"Tchalla AE","year":"2017","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc15-1588"},{"issue":"12","key":"e_1_2_5_42_1","first-page":"4313","article-title":"Elevated concentrations of circulating adhesion molecules and their association with microvascular complications in insulin\u2010dependent diabetes mellitus","volume":"81","author":"Fasching P","year":"1996","journal-title":"J Clin Endocrinol Metab"},{"key":"e_1_2_5_43_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.291.16.1978"},{"key":"e_1_2_5_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2006.09.016"},{"key":"e_1_2_5_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-018-1195-5"},{"key":"e_1_2_5_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2007.04506.x"},{"key":"e_1_2_5_47_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ALC.0000166944.79914.0A"},{"key":"e_1_2_5_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2017.188"},{"key":"e_1_2_5_49_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI60842"},{"key":"e_1_2_5_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2013.04.113"},{"key":"e_1_2_5_51_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.00913"},{"key":"e_1_2_5_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2015.107"},{"key":"e_1_2_5_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jcbfm.9600491"},{"key":"e_1_2_5_54_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00463.2015"},{"key":"e_1_2_5_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.niox.2019.03.006"},{"key":"e_1_2_5_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2016.05.008"},{"key":"e_1_2_5_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2015.10.038"},{"key":"e_1_2_5_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2016.11.005"},{"key":"e_1_2_5_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1382"},{"key":"e_1_2_5_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10600"},{"key":"e_1_2_5_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1744"},{"key":"e_1_2_5_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature16932"},{"key":"e_1_2_5_63_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glv008"},{"key":"e_1_2_5_64_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000013836.85741.17"},{"key":"e_1_2_5_65_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00416.2017"},{"key":"e_1_2_5_66_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12458"},{"key":"e_1_2_5_67_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.02-1049fje"},{"key":"e_1_2_5_68_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01276.2010"},{"key":"e_1_2_5_69_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep39501"},{"key":"e_1_2_5_70_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.109.215483"},{"key":"e_1_2_5_71_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12247"},{"key":"e_1_2_5_72_1","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2011.101"},{"key":"e_1_2_5_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2012.09.008"},{"key":"e_1_2_5_74_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1448"},{"key":"e_1_2_5_75_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00377.2014"},{"key":"e_1_2_5_76_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.102020"},{"key":"e_1_2_5_77_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.102015"},{"key":"e_1_2_5_78_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.116.003806"},{"key":"e_1_2_5_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2019.02.010"},{"key":"e_1_2_5_80_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.115.001770"},{"key":"e_1_2_5_81_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13104-017-2399-x"},{"key":"e_1_2_5_82_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2015.06.001"},{"key":"e_1_2_5_83_1","doi-asserted-by":"publisher","DOI":"10.1186\/2045-824X-4-12"},{"key":"e_1_2_5_84_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2007.07.002"},{"key":"e_1_2_5_85_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijdevneu.2008.10.002"}],"container-title":["Basic &amp; Clinical Pharmacology &amp; Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbcpt.13403","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcpt.13403","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bcpt.13403","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcpt.13403","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T08:17:32Z","timestamp":1693901852000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bcpt.13403"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,23]]},"references-count":84,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2020,8]]}},"alternative-id":["10.1111\/bcpt.13403"],"URL":"https:\/\/doi.org\/10.1111\/bcpt.13403","archive":["Portico"],"relation":{},"ISSN":["1742-7835","1742-7843"],"issn-type":[{"value":"1742-7835","type":"print"},{"value":"1742-7843","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,23]]},"assertion":[{"value":"2020-01-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-03-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-03-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}