{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T10:23:00Z","timestamp":1789035780860,"version":"build-2803163510"},"reference-count":72,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,7]],"date-time":"2022-12-07T00:00:00Z","timestamp":1670371200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical-Scientific Fund of the Mayor of Vienna","award":["AP15115"],"award-info":[{"award-number":["AP15115"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Thoracic aortic aneurysm (TAA) is an age-related and life-threatening vascular disease. Telomere shortening is a predictor of age-related diseases, and its progression is associated with premature vascular disease. The aim of the present work was to investigate the impacts of chronic hypoxia and telomeric DNA damage on cellular homeostasis and vascular degeneration of TAA. We analyzed healthy and aortic aneurysm specimens (215 samples) for telomere length (TL), chronic DNA damage, and resulting changes in cellular homeostasis, focusing on senescence and apoptosis. Compared with healthy thoracic aorta (HTA), patients with tricuspid aortic valve (TAV) showed telomere shortening with increasing TAA size, in contrast to genetically predisposed bicuspid aortic valve (BAV). In addition, TL was associated with chronic hypoxia and telomeric DNA damage and with the induction of senescence-associated secretory phenotype (SASP). TAA-TAV specimens showed a significant difference in SASP-marker expression of IL-6, NF-\u03baB, mTOR, and cell-cycle regulators (\u03b3H2AX, Rb, p53, p21), compared to HTA and TAA-BAV. Furthermore, we observed an increase in CD163+ macrophages and a correlation between hypoxic DNA damage and the number of aortic telocytes. We conclude that chronic hypoxia is associated with telomeric DNA damage and the induction of SASP in a diseased aortic wall, promising a new therapeutic target.<\/jats:p>","DOI":"10.3390\/ijms232415498","type":"journal-article","created":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T01:44:31Z","timestamp":1670463871000},"page":"15498","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Impacts of Telomeric Length, Chronic Hypoxia, Senescence, and Senescence-Associated Secretory Phenotype on the Development of Thoracic Aortic Aneurysm"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3373-8194","authenticated-orcid":false,"given":"Thomas","family":"Aschacher","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Surgery, Clinic Floridsdorf and Karl Landsteiner Institute for Cardio-Vascular Research, 1210 Vienna, Austria"},{"name":"Department of Cardiac Surgery, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Geisler","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Clinic Floridsdorf and Karl Landsteiner Institute for Cardio-Vascular Research, 1210 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verena","family":"Lenz","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Clinic Floridsdorf and Karl Landsteiner Institute for Cardio-Vascular Research, 1210 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Aschacher","sequence":"additional","affiliation":[{"name":"Department of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"Winkler","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Clinic Floridsdorf and Karl Landsteiner Institute for Cardio-Vascular Research, 1210 Vienna, Austria"},{"name":"Faculty of Medicine, Sigmund Freud Private University of Vienna, 1030 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9268-2461","authenticated-orcid":false,"given":"Anne-Kristin","family":"Schaefer","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Mitterbauer","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigitte","family":"Wolf","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7200-4145","authenticated-orcid":false,"given":"Florian K.","family":"Enzmann","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8331-6497","authenticated-orcid":false,"given":"Barbara","family":"Messner","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7257-110X","authenticated-orcid":false,"given":"G\u00fcnther","family":"Laufer","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek P.","family":"Ehrlich","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Grabenw\u00f6ger","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Clinic Floridsdorf and Karl Landsteiner Institute for Cardio-Vascular Research, 1210 Vienna, Austria"},{"name":"Faculty of Medicine, Sigmund Freud Private University of Vienna, 1030 Vienna, 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(2017). Telomere Biology and Thoracic Aortic Aneurysm. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19010003"},{"key":"ref_2","first-page":"993","article-title":"Decreased vascular smooth muscle cell density in medial degeneration of human abdominal aortic aneurysms","volume":"150","author":"Holmes","year":"1997","journal-title":"Am. J. Pathol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/S0002-9149(77)80005-2","article-title":"Pathogenesis of dissecting aneurysm of aorta. Comparative histopathologic study of significance of medial changes","volume":"39","author":"Schlatmann","year":"1977","journal-title":"Am. J. Cardiol."},{"key":"ref_4","first-page":"H781","article-title":"Role of vasa vasorum in nourishment of the aortic wall","volume":"240","author":"Heistad","year":"1981","journal-title":"Am. J. Physiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"124","DOI":"10.3389\/fcvm.2018.00124","article-title":"Medial Hypoxia and Adventitial Vasa Vasorum Remodeling in Human Ascending Aortic Aneurysm","volume":"5","author":"Billaud","year":"2018","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Cafueri, G., Parodi, F., Pistorio, A., Bertolotto, M., Ventura, F., Gambini, C., Bianco, P., Dallegri, F., Pistoia, V., and Pezzolo, A. (2012). Endothelial and smooth muscle cells from abdominal aortic aneurysm have increased oxidative stress and telomere attrition. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0035312"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.atherosclerosis.2011.11.035","article-title":"Characteristics of TAV- and BAV-associated thoracic aortic aneurysms-smooth muscle cell biology, expression profiling, and histological analyses","volume":"220","author":"Blunder","year":"2012","journal-title":"Atherosclerosis"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"6622","DOI":"10.1073\/pnas.85.18.6622","article-title":"A highly conserved repetitive DNA sequence, (TTAGGG)n, present at the telomeres of human chromosomes","volume":"85","author":"Moyzis","year":"1988","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/0968-0004(91)90155-O","article-title":"Telomeres","volume":"16","author":"Blackburn","year":"1991","journal-title":"Trends Biochem. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1146\/annurev.genet.41.110306.130350","article-title":"How shelterin protects mammalian telomeres","volume":"42","author":"Palm","year":"2008","journal-title":"Annu. Rev. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2446","DOI":"10.1126\/science.1069523","article-title":"Senescence induced by altered telomere state, not telomere loss","volume":"295","author":"Karlseder","year":"2002","journal-title":"Science"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1146\/annurev-genet-032918-021921","article-title":"Shelterin-Mediated Telomere Protection","volume":"52","year":"2018","journal-title":"Annu. Rev. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1083\/jcb.146.5.905","article-title":"Megabase chromatin domains involved in DNA double-strand breaks in vivo","volume":"146","author":"Rogakou","year":"1999","journal-title":"J. Cell Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1038\/nrc2523","article-title":"GammaH2AX and cancer","volume":"8","author":"Bonner","year":"2008","journal-title":"Nat. Rev. Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/345458a0","article-title":"Telomeres shorten during ageing of human fibroblasts","volume":"345","author":"Harley","year":"1990","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"102956","DOI":"10.1016\/j.dnarep.2020.102956","article-title":"The role of telomeres and telomerase in the senescence of postmitotic cells","volume":"95","author":"Panczyszyn","year":"2020","journal-title":"DNA Repair"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.ebiom.2017.03.027","article-title":"Telomeres and cell senescence-size matters not","volume":"21","author":"Victorelli","year":"2017","journal-title":"EBioMedicine"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.molmed.2010.03.003","article-title":"Inflammatory networks during cellular senescence: Causes and consequences","volume":"16","author":"Freund","year":"2010","journal-title":"Trends Mol. Med."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Sun, L., Yu, R., and Dang, W. (2018). Chromatin Architectural Changes during Cellular Senescence and Aging. Genes, 9.","DOI":"10.3390\/genes9040211"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/S0092-8674(03)00401-X","article-title":"Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence","volume":"113","author":"Narita","year":"2003","journal-title":"Cell"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1126\/science.aaa5612","article-title":"The DNA damage response induces inflammation and senescence by inhibiting autophagy of GATA4","volume":"349","author":"Kang","year":"2015","journal-title":"Science"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/2046-2395-3-1","article-title":"Telomeres, oxidative stress and inflammatory factors: Partners in cellular senescence?","volume":"3","author":"Hewitt","year":"2014","journal-title":"Longev. Healthspan"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.1038\/nm.4000","article-title":"Cellular senescence in aging and age-related disease: From mechanisms to therapy","volume":"21","author":"Childs","year":"2015","journal-title":"Nat. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1016\/j.molcel.2016.01.028","article-title":"The Mitochondrial Basis of Aging","volume":"61","author":"Sun","year":"2016","journal-title":"Mol. Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1038\/nrg1656","article-title":"Telomeres and human disease: Ageing, cancer and beyond","volume":"6","author":"Blasco","year":"2005","journal-title":"Nat. Rev. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1196\/annals.1297.047","article-title":"Mechanism of telomere shortening by oxidative stress","volume":"1019","author":"Kawanishi","year":"2004","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.mad.2018.03.013","article-title":"The impact of oxidative DNA damage and stress on telomere homeostasis","volume":"177","author":"Barnes","year":"2019","journal-title":"Mech. Ageing Dev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1038\/ncomms1708","article-title":"Telomeres are favoured targets of a persistent DNA damage response in ageing and stress-induced senescence","volume":"3","author":"Hewitt","year":"2012","journal-title":"Nat. Commun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/S0968-0004(02)02110-2","article-title":"Oxidative stress shortens telomeres","volume":"27","year":"2002","journal-title":"Trends Biochem. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"563","DOI":"10.5830\/CVJA-2012-056","article-title":"Telomeres and atherosclerosis","volume":"23","author":"Khan","year":"2012","journal-title":"Cardiovasc. J. Afr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2034","DOI":"10.1161\/01.CIR.0000093661.90582.c4","article-title":"Oxidative stress and cardiovascular injury: Part II: Animal and human studies","volume":"108","author":"Griendling","year":"2003","journal-title":"Circulation"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.atherosclerosis.2008.03.029","article-title":"Inhibition of reactive oxygen species attenuates aneurysm formation in a murine model","volume":"202","author":"Xiong","year":"2009","journal-title":"Atherosclerosis"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"R1","DOI":"10.1530\/ERP-19-0049","article-title":"A review of thoracic aortic aneurysm disease","volume":"7","author":"Clift","year":"2020","journal-title":"Echo Res. Pract."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1139\/g89-104","article-title":"Recognition and elongation of telomeres by telomerase","volume":"31","author":"Blackburn","year":"1989","journal-title":"Genome"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Badran, A., Nasser, S.A., Mesmar, J., El-Yazbi, A.F., Bitto, A., Fardoun, M.M., Baydoun, E., and Eid, A.H. (2020). Reactive Oxygen Species: Modulators of Phenotypic Switch of Vascular Smooth Muscle Cells. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21228764"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1093\/eurheartj\/ehr304","article-title":"Nitric oxide synthases: Regulation and function","volume":"33","author":"Forstermann","year":"2012","journal-title":"Eur. Heart J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1002\/(SICI)1096-9896(200002)190:3<244::AID-PATH575>3.0.CO;2-8","article-title":"Nitric oxide in the pathogenesis of vascular disease","volume":"190","author":"Li","year":"2000","journal-title":"J. Pathol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.4161\/cc.8.12.8865","article-title":"The apoptotic ring: A novel entity with phosphorylated histones H2AX and H2B and activated DNA damage response kinases","volume":"8","author":"Solier","year":"2009","journal-title":"Cell Cycle"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1242\/jcs.092262","article-title":"Chronic hypoxia compromises repair of DNA double-strand breaks to drive genetic instability","volume":"125","author":"Kumareswaran","year":"2012","journal-title":"J. Cell Sci."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Ramirez, R., Ceprian, N., Figuer, A., Valera, G., Bodega, G., Alique, M., and Carracedo, J. (2022). Endothelial Senescence and the Chronic Vascular Diseases: Challenges and Therapeutic Opportunities in Atherosclerosis. J. Pers. Med., 12.","DOI":"10.3390\/jpm12020215"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1038\/ncb3225","article-title":"mTOR regulates MAPKAPK2 translation to control the senescence-associated secretory phenotype","volume":"17","author":"Herranz","year":"2015","journal-title":"Nat. Cell Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2125","DOI":"10.1101\/gad.17276711","article-title":"Control of the senescence-associated secretory phenotype by NF-kappaB promotes senescence and enhances chemosensitivity","volume":"25","author":"Chien","year":"2011","journal-title":"Genes Dev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1172\/JCI64098","article-title":"Cellular senescence and the senescent secretory phenotype: Therapeutic opportunities","volume":"123","author":"Tchkonia","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Martinez de Toda, I., Ceprian, N., Diaz-Del Cerro, E., and De la Fuente, M. (2021). The Role of Immune Cells in Oxi-Inflamm-Aging. Cells, 10.","DOI":"10.3390\/cells10112974"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"9697","DOI":"10.1111\/jcmm.16919","article-title":"Telocytes in the human ascending aorta: Characterization and exosome-related KLF-4\/VEGF-A expression","volume":"25","author":"Aschacher","year":"2021","journal-title":"J. Cell. Mol. Med."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Aschacher, T., Aschacher, O., Schmidt, K., Enzmann, F.K., Eichmair, E., Winkler, B., Arnold, Z., Nagel, F., Podesser, B.K., and Mitterbauer, A. (2022). The Role of Telocytes and Telocyte-Derived Exosomes in the Development of Thoracic Aortic Aneurysm. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23094730"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/1743-8977-9-21","article-title":"Oxidative stress-induced telomeric erosion as a mechanism underlying airborne particulate matter-related cardiovascular disease","volume":"9","author":"Grahame","year":"2012","journal-title":"Part. Fibre Toxicol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Huusko, T.J., Santaniemi, M., Kakko, S., Taskinen, P., Ukkola, O., Kesaniemi, Y.A., Savolainen, M.J., and Salonurmi, T. (2012). Long telomeres in blood leukocytes are associated with a high risk of ascending aortic aneurysm. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0050828"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1089\/rej.2011.1273","article-title":"Is the mean blood leukocyte telomere length a predictor for sporadic thoracic aortic aneurysm? Data from a preliminary study","volume":"15","author":"Balistreri","year":"2012","journal-title":"Rejuvenation Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"R13","DOI":"10.1530\/VB-19-0027","article-title":"The genetics and biomechanics of thoracic aortic diseases","volume":"1","author":"Harky","year":"2019","journal-title":"Vasc. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"111256","DOI":"10.1016\/j.mad.2020.111256","article-title":"Long-lived post-mitotic cell aging: Is a telomere clock at play?","volume":"189","author":"Gilson","year":"2020","journal-title":"Mech. Ageing Dev."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1016\/j.molcel.2012.09.006","article-title":"Mitochondria and telomeres: The promiscuous roles of TIN2","volume":"47","author":"Sullivan","year":"2012","journal-title":"Mol. Cell"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1111\/j.1749-6632.2000.tb06651.x","article-title":"Inflamm-aging. An evolutionary perspective on immunosenescence","volume":"908","author":"Franceschi","year":"2000","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"166397","DOI":"10.1016\/j.bbadis.2022.166397","article-title":"Effect of oxidative stress on telomere maintenance in aortic smooth muscle cells","volume":"1868","author":"Gordon","year":"2022","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.ebiom.2019.04.060","article-title":"Seno-destructive smooth muscle cells in the ascending aorta of patients with bicuspid aortic valve disease","volume":"43","author":"Balint","year":"2019","journal-title":"EBioMedicine"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2289","DOI":"10.1007\/s00018-013-1555-2","article-title":"The nuclear gamma-H2AX apoptotic ring: Implications for cancers and autoimmune diseases","volume":"71","author":"Solier","year":"2014","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1093\/mutage\/geq052","article-title":"Molecular mechanisms of micronucleus, nucleoplasmic bridge and nuclear bud formation in mammalian and human cells","volume":"26","author":"Fenech","year":"2011","journal-title":"Mutagenesis"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/0027-5107(95)00235-9","article-title":"p53 accumulates in micronuclei after treatment with a DNA breaking chemical, methylnitrosourea, and with the spindle poison, vinblastine","volume":"352","author":"Granetto","year":"1996","journal-title":"Mutat. Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"108342","DOI":"10.1016\/j.mrrev.2020.108342","article-title":"Micronuclei as biomarkers of DNA damage, aneuploidy, inducers of chromosomal hypermutation and as sources of pro-inflammatory DNA in humans","volume":"786","author":"Fenech","year":"2020","journal-title":"Mutat. Res. Rev. Mutat. Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1101\/gad.290635.116","article-title":"The senescence-associated secretory phenotype induces cellular plasticity and tissue regeneration","volume":"31","author":"Ritschka","year":"2017","journal-title":"Genes Dev."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1007\/s13238-019-0612-5","article-title":"Mitochondrion-processed TERC regulates senescence without affecting telomerase activities","volume":"10","author":"Zheng","year":"2019","journal-title":"Protein Cell"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.mrfmmm.2011.08.011","article-title":"Maintaining the end: Roles of telomere proteins in end-protection, telomere replication and length regulation","volume":"730","author":"Stewart","year":"2012","journal-title":"Mutat. Res."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Billard, P., and Poncet, D.A. (2019). Replication Stress at Telomeric and Mitochondrial DNA: Common Origins and Consequences on Ageing. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20194959"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Zurek, M., Altschmied, J., Kohlgruber, S., Ale-Agha, N., and Haendeler, J. (2016). Role of Telomerase in the Cardiovascular System. Genes, 7.","DOI":"10.3390\/genes7060029"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"78297","DOI":"10.18632\/oncotarget.13049","article-title":"Expression of functional alternative telomerase RNA component gene in mouse brain and in motor neurons cells protects from oxidative stress","volume":"7","author":"Eitan","year":"2016","journal-title":"Oncotarget"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1038\/nrm2233","article-title":"Cellular senescence: When bad things happen to good cells","volume":"8","author":"Campisi","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1111\/cas.13184","article-title":"Impact of senescence-associated secretory phenotype and its potential as a therapeutic target for senescence-associated diseases","volume":"108","author":"Watanabe","year":"2017","journal-title":"Cancer Sci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.neo.2019.11.002","article-title":"Long interspersed element-1 ribonucleoprotein particles protect telomeric ends in alternative lengthening of telomeres dependent cells","volume":"22","author":"Aschacher","year":"2020","journal-title":"Neoplasia"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1593\/tlo.11202","article-title":"Expression of telomeres in astrocytoma WHO grade 2 to 4: TERRA level correlates with telomere length, telomerase activity, and advanced clinical grade","volume":"5","author":"Sampl","year":"2012","journal-title":"Transl. Oncol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e45","DOI":"10.1093\/nar\/29.9.e45","article-title":"A new mathematical model for relative quantification in realtime RTPCR","volume":"29","author":"Pfaffl","year":"2001","journal-title":"Nucleic Acid. Res."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Scola, L., Giarratana, R.M., Marinello, V., Cancila, V., Pisano, C., Ruvolo, G., Frati, G., Lio, D., and Balistreri, C.R. (2021). Polymorphisms of Pro-Inflammatory IL-6 and IL-1beta Cytokines in Ascending Aortic Aneurysms as Genetic Modifiers and Predictive and Prognostic Biomarkers. Biomolecules, 11.","DOI":"10.3390\/biom11070943"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"13316","DOI":"10.1074\/jbc.M609798200","article-title":"leptin-induced growth stimulation of breast cancer cells involves recruitment of histone acetyltransferases and mediator complex to CYCLIN D1 promoter via activation of Stat3","volume":"282","author":"Saxena","year":"2007","journal-title":"J. Biol. Chem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/24\/15498\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:35:49Z","timestamp":1760146549000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/24\/15498"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,7]]},"references-count":72,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["ijms232415498"],"URL":"https:\/\/doi.org\/10.3390\/ijms232415498","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,7]]}}}