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Here, we discovered that the Y-box factor ZONAB (ZO-1-associated nucleic acid binding protein; YBX3), a gene associated with risk loci for severe vascular disorders, regulates endothelial homeostasis and angiogenesis. By combining cell-based assays with primary endothelial cells and genome-wide expression and methylation measurements, we found that ZONAB depletion results in mitochondrial deregulation, increased reactive oxygen species, and a defective oxidative stress response, which correlates with increased promoter methylation of cell cycle genes. ZONAB depletion triggered cellular senescence via a phosphatidylinositol 3-kinase (PI3K)\/Akt-dependent pathway, which was attenuated by PIK3 inhibitors, an antioxidant, or by drugs targeting mitochondrial function or fragmentation. Thus, our results reveal that ZONAB repression in endothelial cells leads to genome-wide changes in gene expression and DNA methylation, regulating endothelial proliferation and inflammation, as well as mitochondrial deregulation to promote cellular senescence. Hence, ZONAB supports endothelial homeostasis and may play a role in vascular health.<\/jats:p>","DOI":"10.3390\/cells15111015","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T08:09:16Z","timestamp":1780301356000},"page":"1015","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["ZONAB Regulates DNA Methylation, Mitochondrial Function, and Entry into Cell Senescence of Endothelial Cells"],"prefix":"10.3390","volume":"15","author":[{"given":"Wenyi","family":"Jiang","sequence":"first","affiliation":[{"name":"UCL Institute of Ophthalmology, University College London, London EC1V 9EL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleanor","family":"Lynam","sequence":"additional","affiliation":[{"name":"UCL Institute of Ophthalmology, University College London, London EC1V 9EL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliette","family":"Delafosse","sequence":"additional","affiliation":[{"name":"UCL Institute of Ophthalmology, University College London, London EC1V 9EL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0981-8672","authenticated-orcid":false,"given":"Graeme M.","family":"Birdsey","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute (NHLI), Imperial College London, London W12 0NN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna M.","family":"Randi","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute (NHLI), Imperial College London, London W12 0NN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8026-7220","authenticated-orcid":false,"given":"Karl","family":"Matter","sequence":"additional","affiliation":[{"name":"UCL Institute of Ophthalmology, University College London, London EC1V 9EL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8427-6746","authenticated-orcid":false,"given":"Maria S.","family":"Balda","sequence":"additional","affiliation":[{"name":"UCL Institute of Ophthalmology, University College London, London EC1V 9EL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Georgieva, I., Tchekalarova, J., Iliev, D., and Tzoneva, R. (2023). Endothelial Senescence and Its Impact on Angiogenesis in Alzheimer\u2019s Disease. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241411344"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s12276-022-00906-w","article-title":"Endothelial senescence in vascular diseases: Current understanding and future opportunities in senotherapeutics","volume":"55","author":"Han","year":"2023","journal-title":"Exp. Mol. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1038\/s41581-022-00601-z","article-title":"Cellular senescence: The good, the bad and the unknown","volume":"18","author":"Huang","year":"2022","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1038\/s41588-020-0705-3","article-title":"Population-specific and trans-ancestry genome-wide analyses identify distinct and shared genetic risk loci for coronary artery disease","volume":"52","author":"Koyama","year":"2020","journal-title":"Nat. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1038\/s41588-022-01233-6","article-title":"Discovery and systematic characterization of risk variants and genes for coronary artery disease in over a million participants","volume":"54","author":"Aragam","year":"2022","journal-title":"Nat. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"eadj1182","DOI":"10.1126\/science.adj1182","article-title":"Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program","volume":"385","author":"Verma","year":"2024","journal-title":"Science"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1616","DOI":"10.1038\/s41588-021-00954-4","article-title":"A generalized linear mixed model association tool for biobank-scale data","volume":"53","author":"Jiang","year":"2021","journal-title":"Nat. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2024","DOI":"10.1093\/emboj\/19.9.2024","article-title":"The tight junction protein ZO-1 and an interacting transcription factor regulate ErbB-2 expression","volume":"19","author":"Balda","year":"2000","journal-title":"EMBO J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1083\/jcb.200210020","article-title":"The ZO-1-associated Y-box factor ZONAB regulates epithelial cell proliferation and cell density","volume":"160","author":"Balda","year":"2003","journal-title":"J. Cell Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1681\/ASN.2009070698","article-title":"ZONAB promotes proliferation and represses differentiation of proximal tubule epithelial cells","volume":"21","author":"Lima","year":"2010","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2387","DOI":"10.1128\/MCB.26.6.2387-2398.2006","article-title":"Regulation of PCNA and cyclin D1 expression and epithelial morphogenesis by the ZO-1-regulated transcription factor ZONAB\/DbpA","volume":"26","author":"Sourisseau","year":"2006","journal-title":"Mol. Cell Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1091\/mbc.e05-06-0507","article-title":"The heat-shock protein Apg-2 binds to the tight junction protein ZO-1 and regulates transcriptional activity of ZONAB","volume":"17","author":"Tsapara","year":"2006","journal-title":"Mol. Biol. Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"10897","DOI":"10.1073\/pnas.1118822109","article-title":"Stress- and Rho-activated ZO-1-associated nucleic acid binding protein binding to p21 mRNA mediates stabilization, translation, and cell survival","volume":"109","author":"Nie","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/sj.emboj.7600497","article-title":"RalA interacts with ZONAB in a cell density-dependent manner and regulates its transcriptional activity","volume":"24","author":"Frankel","year":"2005","journal-title":"EMBO J."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Dupasquier, S., Delmarcelle, A.S., Marbaix, E., Cosyns, J.P., Courtoy, P.J., and Pierreux, C.E. (2014). Validation of housekeeping gene and impact on normalized gene expression in clear cell renal cell carcinoma: Critical reassessment of YBX3\/ZONAB\/CSDA expression. BMC Mol. Biol., 15.","DOI":"10.1186\/1471-2199-15-9"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1158\/1541-7786.MCR-07-0198","article-title":"Phosphatidylethanol accumulation promotes intestinal hyperplasia by inducing ZONAB-mediated cell density increase in response to chronic ethanol exposure","volume":"5","author":"Pannequin","year":"2007","journal-title":"Mol. Cancer Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1097\/CM9.0000000000001328","article-title":"Notoginsenoside R1 attenuates breast cancer progression by targeting CCND2 and YBX3","volume":"134","author":"Qin","year":"2021","journal-title":"Chin. Med. J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/s10142-023-01145-6","article-title":"Identification of RNA-binding protein YBX3 as an oncogene in clear cell renal cell carcinoma","volume":"23","author":"Wang","year":"2023","journal-title":"Funct. Integr. Genom."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Sun, Y., Li, Z., Wang, W., Zhang, X., Li, W., Du, G., Yin, J., Xiao, W., and Yang, H. (2022). Identification and verification of YBX3 and its regulatory gene HEIH as an oncogenic system: A multidimensional analysis in colon cancer. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.957865"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3498","DOI":"10.1182\/blood-2007-08-105346","article-title":"Transcription factor Erg regulates angiogenesis and endothelial apoptosis through VE-cadherin","volume":"111","author":"Birdsey","year":"2008","journal-title":"Blood"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Kim, H., and Xue, X. (2020). Detection of Total Reactive Oxygen Species in Adherent Cells by 2\u2032,7\u2032-Dichlorodihydrofluorescein Diacetate Staining. J. Vis. Exp., e60682.","DOI":"10.3791\/60682-v"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"W83","DOI":"10.1093\/nar\/gkae410","article-title":"The Galaxy platform for accessible, reproducible, and collaborative data analyses: 2024 update","volume":"52","author":"Galaxy","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"W501","DOI":"10.1093\/nar\/gkx372","article-title":"Pathview Web: User friendly pathway visualization and data integration","volume":"45","author":"Luo","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1093\/bioinformatics\/btu638","article-title":"HTSeq--a Python framework to work with high-throughput sequencing data","volume":"31","author":"Anders","year":"2015","journal-title":"Bioinformatics"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: Ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3047","DOI":"10.1093\/bioinformatics\/btw354","article-title":"MultiQC: Summarize analysis results for multiple tools and samples in a single report","volume":"32","author":"Ewels","year":"2016","journal-title":"Bioinformatics"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1080\/14789450.2023.2265062","article-title":"A Galaxy of informatics resources for MS-based proteomics","volume":"20","author":"Mehta","year":"2023","journal-title":"Expert Rev. Proteom."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1038\/nbt.1883","article-title":"Full-length transcriptome assembly from RNA-Seq data without a reference genome","volume":"29","author":"Grabherr","year":"2011","journal-title":"Nat. Biotechnol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1093\/bioinformatics\/btt684","article-title":"ChAMP: 450k Chip Analysis Methylation Pipeline","volume":"30","author":"Morris","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1083\/jcb.201404140","article-title":"ZO-1 controls endothelial adherens junctions, cell-cell tension, angiogenesis, and barrier formation","volume":"208","author":"Tornavaca","year":"2015","journal-title":"J. Cell Biol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Normandin, K., Coulombe-Huntington, J., St-Denis, C., Bernard, A., Bourouh, M., Bertomeu, T., Tyers, M., and Archambault, V. (2023). Genetic enhancers of partial PLK1 inhibition reveal hypersensitivity to kinetochore perturbations. PLoS Genet., 19.","DOI":"10.1371\/journal.pgen.1010903"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1038\/onc.2011.394","article-title":"AKT induces senescence in human cells via mTORC1 and p53 in the absence of DNA damage: Implications for targeting mTOR during malignancy","volume":"31","author":"Astle","year":"2012","journal-title":"Oncogene"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1038\/s41418-019-0384-8","article-title":"A functional genetic screen defines the AKT-induced senescence signaling network","volume":"27","author":"Chan","year":"2020","journal-title":"Cell Death Differ."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.cell.2017.04.001","article-title":"AKT\/PKB Signaling: Navigating the Network","volume":"169","author":"Manning","year":"2017","journal-title":"Cell"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Mijit, M., Caracciolo, V., Melillo, A., Amicarelli, F., and Giordano, A. (2020). Role of p53 in the Regulation of Cellular Senescence. Biomolecules, 10.","DOI":"10.3390\/biom10030420"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Terao, R., Ahmed, T., Suzumura, A., and Terasaki, H. (2022). Oxidative Stress-Induced Cellular Senescence in Aging Retina and Age-Related Macular Degeneration. Antioxidants, 11.","DOI":"10.3390\/antiox11112189"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Koundouros, N., and Poulogiannis, G. (2018). Phosphoinositide 3-Kinase\/Akt Signaling and Redox Metabolism in Cancer. Front. Oncol., 8.","DOI":"10.3389\/fonc.2018.00160"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Kasai, S., Shimizu, S., Tatara, Y., Mimura, J., and Itoh, K. (2020). Regulation of Nrf2 by Mitochondrial Reactive Oxygen Species in Physiology and Pathology. Biomolecules, 10.","DOI":"10.3390\/biom10020320"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1038\/s41419-021-04035-6","article-title":"HO-1 nuclear accumulation and interaction with NPM1 protect against stress-induced endothelial senescence independent of its enzymatic activity","volume":"12","author":"Luo","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.18632\/aging.101506","article-title":"Heme oxygenase-1 ameliorates oxidative stress-induced endothelial senescence via regulating endothelial nitric oxide synthase activation and coupling","volume":"10","author":"Luo","year":"2018","journal-title":"Aging"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"D\u2019Egidio, F., Qosja, E., Ammannito, F., Topi, S., d\u2019Angelo, M., Cimini, A., and Castelli, V. (2025). Antioxidant and Anti-Inflammatory Defenses in Huntington\u2019s Disease: Roles of NRF2 and PGC-1alpha, and Therapeutic Strategies. Life, 15.","DOI":"10.20944\/preprints202503.0410.v1"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"22576","DOI":"10.1074\/jbc.M110.118976","article-title":"p62\/SQSTM1 is a target gene for transcription factor NRF2 and creates a positive feedback loop by inducing antioxidant response element-driven gene transcription","volume":"285","author":"Jain","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"884S","DOI":"10.3945\/ajcn.110.001917","article-title":"Regulation of PGC-1alpha, a nodal regulator of mitochondrial biogenesis","volume":"93","author":"Auwerx","year":"2011","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Uchikado, Y., Ikeda, Y., and Ohishi, M. (2022). Current Understanding of the Pivotal Role of Mitochondrial Dynamics in Cardiovascular Diseases and Senescence. Front. Cardiovasc. Med., 9.","DOI":"10.3389\/fcvm.2022.905072"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e158447","DOI":"10.1172\/JCI158447","article-title":"Mitochondrial dysfunction in cell senescence and aging","volume":"132","author":"Miwa","year":"2022","journal-title":"J. Clin. Investig."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2451","DOI":"10.1096\/fj.201901747RR","article-title":"p53 regulates mitochondrial dynamics by inhibiting Drp1 translocation into mitochondria during cellular senescence","volume":"34","author":"Kim","year":"2020","journal-title":"FASEB J."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Araujo, A.P.B., Vargas, G., Hayashide, L.S., Matias, I., Andrade, C.B.V., de Carvalho, J.J., Gomes, F.C.A., and Diniz, L.P. (2024). Aging promotes an increase in mitochondrial fragmentation in astrocytes. Front. Cell Neurosci., 18.","DOI":"10.3389\/fncel.2024.1496163"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"101904","DOI":"10.1016\/j.mito.2024.101904","article-title":"Multifaceted role of dynamin-related protein 1 in cardiovascular disease: From mitochondrial fission to therapeutic interventions","volume":"78","author":"Kaur","year":"2024","journal-title":"Mitochondrion"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1093\/hmg\/ddy335","article-title":"Mitochondrial division inhibitor 1 reduces dynamin-related protein 1 and mitochondrial fission activity","volume":"28","author":"Manczak","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1038\/ncb2879","article-title":"Senescent cells harbour features of the cancer epigenome","volume":"15","author":"Cruickshanks","year":"2013","journal-title":"Nat. Cell Biol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Crouch, J., Shvedova, M., Thanapaul, R., Botchkarev, V., and Roh, D. (2022). Epigenetic Regulation of Cellular Senescence. Cells, 11.","DOI":"10.3390\/cells11040672"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.18632\/aging.100988","article-title":"FOXM1 regulates proliferation, senescence and oxidative stress in keratinocytes and cancer cells","volume":"8","author":"Smirnov","year":"2016","journal-title":"Aging"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/s12195-014-0371-6","article-title":"Endothelial Cell Senescence Increases Traction Forces due to Age-Associated Changes in the Glycocalyx and SIRT1","volume":"8","author":"Cheung","year":"2015","journal-title":"Cell Mol. Bioeng."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Ferrari, S., and Pesce, M. (2021). Stiffness and Aging in Cardiovascular Diseases: The Dangerous Relationship between Force and Senescence. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22073404"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1083\/jcb.200302070","article-title":"Size-selective loosening of the blood-brain barrier in claudin-5-deficient mice","volume":"161","author":"Nitta","year":"2003","journal-title":"J. Cell Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1161\/STROKEAHA.115.010835","article-title":"Vascular Cell Senescence Contributes to Blood-Brain Barrier Breakdown","volume":"47","author":"Yamazaki","year":"2016","journal-title":"Stroke"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2470482","DOI":"10.1080\/21688370.2025.2470482","article-title":"Claudin-1 impairs blood-brain barrier by downregulating endothelial junctional proteins in traumatic brain injury","volume":"13","author":"Gowrikumar","year":"2025","journal-title":"Tissue Barriers"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1007\/s00401-011-0883-2","article-title":"Claudin-1 induced sealing of blood-brain barrier tight junctions ameliorates chronic experimental autoimmune encephalomyelitis","volume":"122","author":"Pfeiffer","year":"2011","journal-title":"Acta Neuropathol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3769","DOI":"10.1038\/s41598-017-04005-z","article-title":"Nuclear accumulation of symplekin promotes cellular proliferation and dedifferentiation in an ERK1\/2-dependent manner","volume":"7","author":"Zhang","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"703","DOI":"10.3892\/ijmm.2016.2662","article-title":"RNAi-mediated downregulation of DNA binding protein A inhibits tumorigenesis in colorectal cancer","volume":"38","author":"Liu","year":"2016","journal-title":"Int. J. Mol. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2628","DOI":"10.1073\/pnas.0903747107","article-title":"Symplekin promotes tumorigenicity by up-regulating claudin-2 expression","volume":"107","author":"Buchert","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2953","DOI":"10.21037\/tau-2025-328","article-title":"Single-cell multi-omics and spatial transcriptomics reveal the transcriptional regulatory landscape of clear cell renal cell carcinoma","volume":"14","author":"Duan","year":"2025","journal-title":"Transl. Androl. Urol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Georgiadis, A., Tschernutter, M., Bainbridge, J.W., Balaggan, K.S., Mowat, F., West, E.L., Munro, P.M., Thrasher, A.J., Matter, K., and Balda, M.S. (2010). The tight junction associated signalling proteins ZO-1 and ZONAB regulate retinal pigment epithelium homeostasis in mice. PLoS ONE, 5, Correction in PLoS ONE 2023, 18, e0295782.","DOI":"10.1371\/journal.pone.0295782"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.trsl.2025.12.001","article-title":"ZONAB regulates renal cyst formation in nphp1 knockout mice","volume":"285\u2013286","author":"Lai","year":"2025","journal-title":"Transl. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e202000980","DOI":"10.26508\/lsa.202000980","article-title":"Cyclin A2 localises in the cytoplasm at the S\/G2 transition to activate PLK1","volume":"4","author":"Burdova","year":"2021","journal-title":"Life Sci. Alliance"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"4012","DOI":"10.18632\/aging.204743","article-title":"Key elements of cellular senescence involve transcriptional repression of mitotic and DNA repair genes through the p53-p16\/RB-E2F-DREAM complex","volume":"15","author":"Tchkonia","year":"2023","journal-title":"Aging"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1093\/gerona\/glt017","article-title":"Downregulation of Polo-like kinase 1 induces cellular senescence in human primary cells through a p53-dependent pathway","volume":"68","author":"Kim","year":"2013","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"189","DOI":"10.2174\/1566523211313030004","article-title":"Impact of PLK-1 silencing on endothelial cells and cancer cells of diverse histological origin","volume":"13","author":"Gomes","year":"2013","journal-title":"Curr. Gene Ther."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Ward, A., and Hudson, J.W. (2014). p53-Dependent and cell specific epigenetic regulation of the polo-like kinases under oxidative stress. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0087918"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Xu, H., Li, S., and Liu, Y.S. (2021). Roles and Mechanisms of DNA Methylation in Vascular Aging and Related Diseases. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.699374"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Sun, X., and Feinberg, M.W. (2021). Vascular Endothelial Senescence: Pathobiological Insights, Emerging Long Noncoding RNA Targets, Challenges and Therapeutic Opportunities. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.693067"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1080\/15384101.2017.1282585","article-title":"The role of WRNIP1 in genome maintenance","volume":"16","author":"Yoshimura","year":"2017","journal-title":"Cell Cycle"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2834","DOI":"10.1038\/s41467-018-05258-6","article-title":"FoxM1 repression during human aging leads to mitotic decline and aneuploidy-driven full senescence","volume":"9","author":"Macedo","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Shentu, T.P., Wu, T., Zhou, Z., Yeh, C.F., Zhu, J., Li, J., Miao, B.A., Lee, T.H., Zhang, L., and Huang, R.T. (2025). Mechanosensitive Endothelial METTL7A Regulates Internal m (7) G mRNA Methylation and Protects Against Atherosclerosis. bioRxiv, preprint.","DOI":"10.1101\/2025.05.22.655328"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"5304","DOI":"10.1039\/D2NA00424K","article-title":"Snapshot imprinting as a tool for surface mapping and identification of novel biomarkers of senescent cells","volume":"4","author":"Piletska","year":"2022","journal-title":"Nanoscale Adv."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1007\/s11357-019-00074-2","article-title":"Nicotinamide mononucleotide (NMN) treatment attenuates oxidative stress and rescues angiogenic capacity in aged cerebromicrovascular endothelial cells: A potential mechanism for the prevention of vascular cognitive impairment","volume":"41","author":"Kiss","year":"2019","journal-title":"Geroscience"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1186\/s12987-022-00370-8","article-title":"ROS attenuates TET2-dependent ZO-1 epigenetic expression in cerebral vascular endothelial cells","volume":"19","author":"Wang","year":"2022","journal-title":"Fluids Barriers CNS"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1186\/s12967-023-04315-z","article-title":"Impaired angiogenesis in ageing: The central role of the extracellular matrix","volume":"21","author":"Xiao","year":"2023","journal-title":"J. Transl. Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e1800242024","DOI":"10.1523\/JNEUROSCI.1800-24.2024","article-title":"Transcription Factor-Wide Association Studies to Identify Functional SNPs in Alzheimer\u2019s Disease","volume":"45","author":"Dunn","year":"2025","journal-title":"J. Neurosci."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/11\/1015\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T04:23:25Z","timestamp":1780374205000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/11\/1015"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,31]]},"references-count":80,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["cells15111015"],"URL":"https:\/\/doi.org\/10.3390\/cells15111015","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,31]]}}}