{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T18:30:18Z","timestamp":1793212218813,"version":"4.5.0"},"reference-count":72,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T00:00:00Z","timestamp":1719273600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T00:00:00Z","timestamp":1719273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["098291\/Z\/12\/Z"],"award-info":[{"award-number":["098291\/Z\/12\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["221699\/Z\/20\/Z"],"award-info":[{"award-number":["221699\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["081172\/Z\/06\/Z"],"award-info":[{"award-number":["081172\/Z\/06\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["FS\/IBSRF\/22\/25121"],"award-info":[{"award-number":["FS\/IBSRF\/22\/25121"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["IG\/17\/2\/32993"],"award-info":[{"award-number":["IG\/17\/2\/32993"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011102","name":"EC | Seventh Framework Programme","doi-asserted-by":"publisher","award":["PCOFUND-GA-2013-608765"],"award-info":[{"award-number":["PCOFUND-GA-2013-608765"]}],"id":[{"id":"10.13039\/100011102","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000317","name":"Action Medical Research","doi-asserted-by":"publisher","award":["GN 2272"],"award-info":[{"award-number":["GN 2272"]}],"id":[{"id":"10.13039\/501100000317","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C16420\/A18066"],"award-info":[{"award-number":["C16420\/A18066"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["EMBO Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cellular senescence is a hallmark of advanced age and a major instigator of numerous inflammatory pathologies. While endothelial cell (EC) senescence is aligned with defective vascular functionality, its impact on fundamental inflammatory responses in vivo at single-cell level remain unclear. To directly investigate the role of EC senescence on dynamics of neutrophil-venular wall interactions, we applied high resolution confocal intravital microscopy to inflamed tissues of an EC-specific progeroid mouse model, characterized by profound indicators of EC senescence. Progerin-expressing ECs supported prolonged neutrophil adhesion and crawling in a cell autonomous manner that additionally mediated neutrophil-dependent microvascular leakage. Transcriptomic and immunofluorescence analysis of inflamed tissues identified elevated levels of EC CXCL1 on progerin-expressing ECs and functional blockade of CXCL1 suppressed the dysregulated neutrophil responses elicited by senescent ECs. Similarly, cultured progerin-expressing human ECs exhibited a senescent phenotype, were pro-inflammatory and prompted increased neutrophil attachment and activation. Collectively, our findings support the concept that senescent ECs drive excessive inflammation and provide new insights into the mode, dynamics, and mechanisms of this response at single-cell level.<\/jats:p>","DOI":"10.1038\/s44319-024-00182-x","type":"journal-article","created":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T13:03:01Z","timestamp":1719320581000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Senescent endothelial cells promote pathogenic neutrophil trafficking in inflamed tissues"],"prefix":"10.1038","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7617-0768","authenticated-orcid":false,"given":"Lo\u00efc","family":"Rolas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monja","family":"Stein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Barkaway","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Reglero-Real","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Sciacca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Yaseen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haitao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Vazquez-Martinez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Golding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isobel A","family":"Blacksell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1135-6729","authenticated-orcid":false,"given":"Meredith J","family":"Giblin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2769-0171","authenticated-orcid":false,"given":"Edyta","family":"Jaworska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cleo L","family":"Bishop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3001-0894","authenticated-orcid":false,"given":"Mathieu-Benoit","family":"Voisin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carles","family":"Gaston-Massuet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliane","family":"Fossati-Jimack","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Costantino","family":"Pitzalis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dianne","family":"Cooper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas D","family":"Nightingale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6964-1904","authenticated-orcid":false,"given":"Carlos","family":"Lopez-Otin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myles J","family":"Lewis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5677-1806","authenticated-orcid":false,"given":"Sussan","family":"Nourshargh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,6,25]]},"reference":[{"key":"182_CR1","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1038\/nature16932","volume":"530","author":"DJ Baker","year":"2016","unstructured":"Baker DJ, Childs BG, Durik M, Wijers ME, Sieben CJ, Zhong J, Saltness RA, Jeganathan KB, Verzosa GC, Pezeshki A et al (2016) Naturally occurring p16Ink4a-positive cells shorten healthy lifespan. Nature 530:184\u2013189","journal-title":"Nature"},{"key":"182_CR2","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1038\/nature10600","volume":"479","author":"DJ Baker","year":"2011","unstructured":"Baker DJ, Wijshake T, Tchkonia T, Lebrasseur NK, Childs BG, Van De Sluis B, Kirkland JL, Van Deursen JM (2011) Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature 479:232\u2013236","journal-title":"Nature"},{"key":"182_CR3","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-14387-w","volume":"11","author":"AJ Barinda","year":"2020","unstructured":"Barinda AJ, Ikeda K, Nugroho DB, Wardhana DA, Sasaki N, Honda S, Urata R, Matoba S, Hirata K-I, Emoto N (2020) Publisher Correction: Endothelial progeria induces adipose tissue senescence and impairs insulin sensitivity through senescence associated secretory phenotype. Nat Commun 11:481","journal-title":"Nat Commun"},{"key":"182_CR4","doi-asserted-by":"publisher","first-page":"1494","DOI":"10.1016\/j.immuni.2021.04.025","volume":"54","author":"A Barkaway","year":"2021","unstructured":"Barkaway A, Rolas L, Joulia R, Bodkin J, Lenn T, Owen-Woods C, Reglero-Real N, Stein M, V\u00e1zquez-Mart\u00ednez L, Girbl T et al (2021) Age-related changes in the local milieu of inflamed tissues cause aberrant neutrophil trafficking and subsequent remote organ damage. Immunity 54:1494\u20131510.e1497","journal-title":"Immunity"},{"key":"182_CR5","doi-asserted-by":"publisher","first-page":"1201","DOI":"10.3390\/cells9051201","volume":"9","author":"G Bidault","year":"2020","unstructured":"Bidault G, Garcia M, Capeau J, Morichon R, Vigouroux C, B\u00e9r\u00e9ziat V (2020) Progerin expression induces inflammation, oxidative stress and senescence in human coronary endothelial cells. Cells 9:1201","journal-title":"Cells"},{"key":"182_CR6","doi-asserted-by":"publisher","DOI":"10.1126\/science.aay5356","volume":"369","author":"F Binet","year":"2020","unstructured":"Binet F, Cagnone G, Crespo-Garcia S, Hata M, Neault M, Dejda A, Wilson AM, Buscarlet M, Mawambo GT, Howard JP et al (2020) Neutrophil extracellular traps target senescent vasculature for tissue remodeling in retinopathy. Science 369:eaay5356","journal-title":"Science"},{"key":"182_CR7","doi-asserted-by":"publisher","first-page":"4373","DOI":"10.1007\/s00018-014-1691-3","volume":"71","author":"DGA Burton","year":"2014","unstructured":"Burton DGA, Krizhanovsky V (2014) Physiological and pathological consequences of cellular senescence. Cell Mol Life Sci 71:4373\u20134386","journal-title":"Cell Mol Life Sci"},{"key":"182_CR8","doi-asserted-by":"publisher","first-page":"eabe4832","DOI":"10.1126\/science.abe4832","volume":"373","author":"CD Camell","year":"2021","unstructured":"Camell CD, Yousefzadeh MJ, Zhu Y, Prata LGPL, Huggins MA, Pierson M, Zhang L, O\u2019Kelly RD, Pirtskhalava T, Xun P et al (2021) Senolytics reduce coronavirus-related mortality in old mice. Science 373:eabe4832","journal-title":"Science"},{"key":"182_CR9","doi-asserted-by":"publisher","first-page":"2833","DOI":"10.1172\/JCI43578","volume":"121","author":"K Cao","year":"2011","unstructured":"Cao K, Blair CD, Faddah DA, Kieckhaefer JE, Olive M, Erdos MR, Nabel EG, Collins FS (2011) Progerin and telomere dysfunction collaborate to trigger cellular senescence in normal human fibroblasts. J Clin Investig 121:2833\u20132844","journal-title":"J Clin Investig"},{"key":"182_CR10","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1242\/dmm.024711","volume":"9","author":"D Carrero","year":"2016","unstructured":"Carrero D, Soria-Valles C, L\u00f3pez-Ot\u00edn C (2016) Hallmarks of progeroid syndromes: lessons from mice and reprogrammed cells. Dis Models Mech 9:719\u2013735","journal-title":"Dis Models Mech"},{"key":"182_CR11","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2020.101073","volume":"62","author":"V Cenni","year":"2020","unstructured":"Cenni V, Capanni C, Mattioli E, Schena E, Squarzoni S, Bacalini MG, Garagnani P, Salvioli S, Franceschi C, Lattanzi G (2020) Lamin A involvement in ageing processes. Ageing Res Rev 62:101073","journal-title":"Ageing Res Rev"},{"key":"182_CR12","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1016\/j.molmed.2020.11.006","volume":"27","author":"L Claesson-Welsh","year":"2021","unstructured":"Claesson-Welsh L, Dejana E, Mcdonald DM (2021) Permeability of the endothelial barrier: identifying and reconciling controversies. Trends Mol Med 27:314\u2013331","journal-title":"Trends Mol Med"},{"key":"182_CR13","doi-asserted-by":"publisher","first-page":"1075","DOI":"10.1016\/j.immuni.2015.05.010","volume":"42","author":"B Colom","year":"2015","unstructured":"Colom B, Bodkin V, Jennifer, Beyrau M, Woodfin A, Ody C, Rourke C, Chavakis T, Brohi K, Imhof AB, Nourshargh S (2015) Leukotriene B4-neutrophil elastase axis drives neutrophil reverse transendothelial cell migration in vivo. Immunity 42:1075\u20131086","journal-title":"Immunity"},{"key":"182_CR14","doi-asserted-by":"publisher","first-page":"1064","DOI":"10.1096\/fj.11-196220","volume":"26","author":"B Colom","year":"2012","unstructured":"Colom B, Poitelon Y, Huang W, Woodfin A, Averill S, Carro UD, Zambroni D, Brain SD, Perretti M, Ahluwalia A et al (2012) Schwann cell\u2010specific JAM\u2010C\u2010deficient mice reveal novel expression and functions for JAM\u2010C in peripheral nerves. FASEB J 26:1064\u20131076","journal-title":"FASEB J"},{"key":"182_CR15","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1146\/annurev-pathol-121808-102144","volume":"5","author":"J-P Copp\u00e9","year":"2010","unstructured":"Copp\u00e9 J-P, Desprez P-Y, Krtolica A, Campisi J (2010) The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu Rev Pathol: Mech Dis 5:99\u2013118","journal-title":"Annu Rev Pathol: Mech Dis"},{"key":"182_CR16","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1016\/j.it.2009.07.012","volume":"30","author":"MR Distasi","year":"2009","unstructured":"Distasi MR, Ley K (2009) Opening the flood-gates: how neutrophil-endothelial interactions regulate permeability. Trends Immunol 30:547\u2013556","journal-title":"Trends Immunol"},{"key":"182_CR17","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1182\/blood.V96.2.719.014k29_719_726","volume":"96","author":"N Faust","year":"2000","unstructured":"Faust N, Varas F, Kelly LM, Heck S, Graf T (2000) Insertion of enhanced green fluorescent protein into the lysozyme gene creates mice with green fluorescent granulocytes and macrophages. Blood 96:719\u2013726","journal-title":"Blood"},{"key":"182_CR18","doi-asserted-by":"publisher","first-page":"1307","DOI":"10.1084\/jem.20132413","volume":"211","author":"M Finsterbusch","year":"2014","unstructured":"Finsterbusch M, Voisin M-B, Beyrau M, Williams TJ, Nourshargh S (2014) Neutrophils recruited by chemoattractants in vivo induce microvascular plasma protein leakage through secretion of TNF. J Exp Med 211:1307\u20131314","journal-title":"J Exp Med"},{"key":"182_CR19","doi-asserted-by":"publisher","first-page":"1062","DOI":"10.1016\/j.immuni.2018.09.018","volume":"49","author":"T Girbl","year":"2018","unstructured":"Girbl T, Lenn T, Perez L, Rolas L, Barkaway A, Thiriot A, Del Fresno C, Lynam E, Hub E, Thelen M et al (2018) Distinct compartmentalization of the chemokines CXCL1 and CXCL2 and the atypical receptor ACKR1 determine discrete stages of neutrophil diapedesis. Immunity 49:1062\u20131076.e1066","journal-title":"Immunity"},{"key":"182_CR20","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1016\/j.cell.2013.12.028","volume":"156","author":"LB Gordon","year":"2014","unstructured":"Gordon LB, Rothman FG, L\u00f3pez-Ot\u00edn C, Misteli T (2014) Progeria: a paradigm for translational medicine. Cell 156:400\u2013407","journal-title":"Cell"},{"key":"182_CR21","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.cmet.2020.05.002","volume":"32","author":"L Grosse","year":"2020","unstructured":"Grosse L, Wagner N, Emelyanov A, Molina C, Lacas-Gervais S, Wagner K-D, Bulavin DV (2020) Defined p16High senescent cell types are indispensable for mouse healthspan. Cell Metab 32:87\u201399.e86","journal-title":"Cell Metab"},{"key":"182_CR22","doi-asserted-by":"publisher","first-page":"925","DOI":"10.1038\/s41590-023-01505-1","volume":"24","author":"GS Gullotta","year":"2023","unstructured":"Gullotta GS, De Feo D, Friebel E, Semerano A, Scotti GM, Bergamaschi A, Butti E, Brambilla E, Genchi A, Capotondo A et al (2023) Age-induced alterations of granulopoiesis generate atypical neutrophils that aggravate stroke pathology. Nat Immunol 24:925\u2013940","journal-title":"Nat Immunol"},{"key":"182_CR23","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201809736","volume":"11","author":"MR Hamczyk","year":"2019","unstructured":"Hamczyk MR, Villa\u2010Bellosta R, Quesada V, Gonzalo P, Vidak S, Nevado RM, Andr\u00e9s\u2010Manzano MJ, Misteli T, L\u00f3pez\u2010Ot\u00edn C, Andr\u00e9s V (2019) Progerin accelerates atherosclerosis by inducing endoplasmic reticulum stress in vascular smooth muscle cells. EMBO Mol Med 11:e9736","journal-title":"EMBO Mol Med"},{"key":"182_CR24","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1016\/j.ebiom.2019.08.069","volume":"47","author":"LJ Hickson","year":"2019","unstructured":"Hickson LJ, Langhi Prata LGP, Bobart SA, Evans TK, Giorgadze N, Hashmi SK, Herrmann SM, Jensen MD, Jia Q, Jordan KL et al (2019) Senolytics decrease senescent cells in humans: preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease. EBioMedicine 47:446\u2013456","journal-title":"EBioMedicine"},{"key":"182_CR25","doi-asserted-by":"publisher","first-page":"1802","DOI":"10.1016\/j.bbadis.2018.08.008","volume":"1865","author":"G Jia","year":"2019","unstructured":"Jia G, Aroor AR, Jia C, Sowers JR (2019) Endothelial cell senescence in aging-related vascular dysfunction. Biochim Biophys Acta Mol Basis Dis 1865:1802\u20131809","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"182_CR26","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1016\/j.ebiom.2018.12.052","volume":"40","author":"JN Justice","year":"2019","unstructured":"Justice JN, Nambiar AM, Tchkonia T, Lebrasseur NK, Pascual R, Hashmi SK, Prata L, Masternak MM, Kritchevsky SB, Musi N et al (2019) Senolytics in idiopathic pulmonary fibrosis: results from a first-in-human, open-label, pilot study. EBioMedicine 40:554\u2013563","journal-title":"EBioMedicine"},{"key":"182_CR27","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1006\/dbio.2000.0106","volume":"230","author":"YY Kisanuki","year":"2001","unstructured":"Kisanuki YY, Hammer RE, Miyazaki J, Williams SC, Richardson JA, Yanagisawa M (2001) Tie2-Cre transgenic mice: a new model for endothelial cell-lineage analysis in vivo. Dev Biol 230:230\u2013242","journal-title":"Dev Biol"},{"key":"182_CR28","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12852","volume":"18","author":"R Kreienkamp","year":"2019","unstructured":"Kreienkamp R, Billon C, Bedia\u2010Diaz G, Albert CJ, Toth Z, Butler AA, Mcbride\u2010Gagyi S, Ford DA, Baldan A, Burris TP et al (2019) Doubled lifespan and patient\u2010like pathologies in progeria mice fed high\u2010fat diet. Aging Cell 18:e12852","journal-title":"Aging Cell"},{"key":"182_CR29","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.ymeth.2015.08.024","volume":"96","author":"N Kubben","year":"2016","unstructured":"Kubben N, Brimacombe KR, Donegan M, Li Z, Misteli T (2016) A high-content imaging-based screening pipeline for the systematic identification of anti-progeroid compounds. Methods 96:46\u201358","journal-title":"Methods"},{"key":"182_CR30","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1038\/s41590-023-01490-5","volume":"24","author":"AJ Kwok","year":"2023","unstructured":"Kwok AJ, Allcock A, Ferreira RC, Cano-Gamez E, Smee M, Burnham KL, Zurke Y-X, Novak A, Darwent M, Baron T et al (2023) Neutrophils and emergency granulopoiesis drive immune suppression and an extreme response endotype during sepsis. Nat Immunol 24:767\u2013779","journal-title":"Nat Immunol"},{"key":"182_CR31","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2020106048","volume":"40","author":"A Lagnado","year":"2021","unstructured":"Lagnado A, Leslie J, Ruchaud\u2010Sparagano MH, Victorelli S, Hirsova P, Ogrodnik M, Collins AL, Vizioli MG, Habiballa L, Saretzki G et al (2021) Neutrophils induce paracrine telomere dysfunction and senescence in ROS\u2010dependent manner. EMBO J 40:e106048","journal-title":"EMBO J"},{"key":"182_CR32","doi-asserted-by":"publisher","first-page":"2949","DOI":"10.1016\/j.ajpath.2015.07.010","volume":"185","author":"CTK Le","year":"2015","unstructured":"Le CTK, Laidlaw G, Morehouse CA, Naiman B, Brohawn P, Mustelin T, Connor JR, Mcdonald DM (2015) Synergistic actions of blocking angiopoietin-2 and tumor necrosis factor-\u03b1 in suppressing remodeling of blood vessels and lymphatics in airway inflammation. Am J Pathol 185:2949\u20132968","journal-title":"Am J Pathol"},{"key":"182_CR33","doi-asserted-by":"publisher","DOI":"10.3389\/fragi.2022.900028","volume":"3","author":"KA Lee","year":"2022","unstructured":"Lee KA, Flores RR, Jang IH, Saathoff A, Robbins PD (2022) Immune senescence, immunosenescence and aging. Front Aging 3:900028","journal-title":"Front Aging"},{"key":"182_CR34","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1038\/nri2156","volume":"7","author":"K Ley","year":"2007","unstructured":"Ley K, Laudanna C, Cybulsky MI, Nourshargh S (2007) Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat Rev Immunol 7:678\u2013689","journal-title":"Nat Rev Immunol"},{"key":"182_CR35","doi-asserted-by":"publisher","first-page":"1194","DOI":"10.1016\/j.cell.2013.05.039","volume":"153","author":"C L\u00f3pez-Ot\u00edn","year":"2013","unstructured":"L\u00f3pez-Ot\u00edn C, Blasco MA, Partridge L, Serrano M, Kroemer G (2013) The hallmarks of aging. Cell 153:1194\u20131217","journal-title":"Cell"},{"key":"182_CR36","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/j.cell.2022.11.001","volume":"186","author":"C L\u00f3pez-Ot\u00edn","year":"2023","unstructured":"L\u00f3pez-Ot\u00edn C, Blasco MA, Partridge L, Serrano M, Kroemer G (2023) Hallmarks of aging: an expanding universe. Cell 186:243\u2013278","journal-title":"Cell"},{"key":"182_CR37","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1038\/nn.2467","volume":"13","author":"L Madisen","year":"2010","unstructured":"Madisen L, Zwingman TA, Sunkin SM, Oh SW, Zariwala HA, Gu H, Ng LL, Palmiter RD, Hawrylycz MJ, Jones AR et al (2010) A robust and high-throughput Cre reporting and characterization system for the whole mouse brain. Nat Neurosci 13:133\u2013140","journal-title":"Nat Neurosci"},{"key":"182_CR38","doi-asserted-by":"publisher","first-page":"1300","DOI":"10.1021\/acscentsci.0c01698","volume":"7","author":"B Marcos-Ramiro","year":"2021","unstructured":"Marcos-Ramiro B, Gil-Ord\u00f3\u00f1ez A, Mar\u00edn-Ramos NI, Ortega-Nogales FJ, Balabasquer M, Gonzalo P, Khiar-Fern\u00e1ndez N, Rolas L, Barkaway A, Nourshargh S et al (2021) Isoprenylcysteine carboxylmethyltransferase-based therapy for Hutchinson\u2013Gilford progeria syndrome. ACS Cent Sci 7:1300\u20131310","journal-title":"ACS Cent Sci"},{"key":"182_CR39","doi-asserted-by":"publisher","first-page":"2016","DOI":"10.1182\/blood-2015-03-631572","volume":"126","author":"S Massena","year":"2015","unstructured":"Massena S, Christoffersson G, V\u00e5gesj\u00f6 E, Seignez C, Gustafsson K, Binet F, Herrera Hidalgo C, Giraud A, Lomei J, Westr\u00f6m S et al (2015) Identification and characterization of VEGF-A-responsive neutrophils expressing CD49d, VEGFR1, and CXCR4 in mice and humans. Blood 126:2016\u20132026","journal-title":"Blood"},{"key":"182_CR40","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1146\/annurev-pathol-020712-164023","volume":"9","author":"TN Mayadas","year":"2014","unstructured":"Mayadas TN, Cullere X, Lowell CA (2014) The multifaceted functions of neutrophils. Annu Rev Pathol: Mech Dis 9:181\u2013218","journal-title":"Annu Rev Pathol: Mech Dis"},{"key":"182_CR41","doi-asserted-by":"publisher","first-page":"e1269","DOI":"10.1371\/journal.pone.0001269","volume":"2","author":"D Mcclintock","year":"2007","unstructured":"Mcclintock D, Ratner D, Lokuge M, Owens DM, Gordon LB, Collins FS, Djabali K (2007) The mutant form of lamin A that causes Hutchinson-Gilford progeria is a biomarker of cellular aging in human skin. PLoS ONE 2:e1269","journal-title":"PLoS ONE"},{"key":"182_CR42","doi-asserted-by":"publisher","first-page":"1541","DOI":"10.1161\/01.CIR.0000013836.85741.17","volume":"105","author":"T Minamino","year":"2002","unstructured":"Minamino T, Miyauchi H, Yoshida T, Ishida Y, Yoshida H, Komuro I (2002) Endothelial cell senescence in human atherosclerosis. Circulation 105:1541\u20131544","journal-title":"Circulation"},{"key":"182_CR43","doi-asserted-by":"publisher","first-page":"1126","DOI":"10.1089\/ars.2012.5149","volume":"20","author":"M Mittal","year":"2014","unstructured":"Mittal M, Siddiqui MR, Tran K, Reddy SP, Malik AB (2014) Reactive oxygen species in inflammation and tissue injury. Antioxid Redox Signal 20:1126\u20131167","journal-title":"Antioxid Redox Signal"},{"key":"182_CR44","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1038\/nrm3823","volume":"15","author":"D Mu\u00f1oz-Esp\u00edn","year":"2014","unstructured":"Mu\u00f1oz-Esp\u00edn D, Serrano M (2014) Cellular senescence: from physiology to pathology. Nat Rev Mol Cell Biol 15:482\u2013496","journal-title":"Nat Rev Mol Cell Biol"},{"key":"182_CR45","first-page":"234","volume":"3","author":"V Nomellini","year":"2012","unstructured":"Nomellini V, Brubaker AL, Mahbub S, Palmer JL, Gomez CR, Kovacs EJ (2012) Dysregulation of neutrophil CXCR2 and pulmonary endothelial icam-1 promotes age-related pulmonary inflammation. Aging Dis 3:234\u2013247","journal-title":"Aging Dis"},{"key":"182_CR46","doi-asserted-by":"publisher","first-page":"1493","DOI":"10.1189\/jlb.1007672","volume":"83","author":"V Nomellini","year":"2008","unstructured":"Nomellini V, Faunce DE, Gomez CR, Kovacs EJ (2008) An age-associated increase in pulmonary inflammation after burn injury is abrogated by CXCR2 inhibition. J Leukoc Biol 83:1493\u20131501","journal-title":"J Leukoc Biol"},{"key":"182_CR47","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1016\/j.immuni.2014.10.008","volume":"41","author":"S Nourshargh","year":"2014","unstructured":"Nourshargh S, Alon R (2014) Leukocyte migration into inflamed tissues. Immunity 41:694\u2013707","journal-title":"Immunity"},{"key":"182_CR48","first-page":"114","volume":"5","author":"R Oakley","year":"2014","unstructured":"Oakley R (2014) Vascular hyperpermeability and aging. Aging Dis 5:114\u2013125","journal-title":"Aging Dis"},{"key":"182_CR49","doi-asserted-by":"publisher","first-page":"2301","DOI":"10.1161\/ATVBAHA.110.209460","volume":"30","author":"M Olive","year":"2010","unstructured":"Olive M, Harten I, Mitchell R, Beers JK, Djabali K, Cao K, Erdos MR, Blair C, Funke B, Smoot L et al (2010) Cardiovascular pathology in Hutchinson-Gilford progeria: correlation with the vascular pathology of aging. Arterioscler Thromb Vasc Biol 30:2301\u20132309","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"182_CR50","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1172\/JCI121297","volume":"129","author":"S Osmanagic-Myers","year":"2018","unstructured":"Osmanagic-Myers S, Kiss A, Manakanatas C, Hamza O, Sedlmayer F, Szabo PL, Fischer I, Fichtinger P, Podesser BK, Eriksson M et al (2018) Endothelial progerin expression causes cardiovascular pathology through an impaired mechanoresponse. J Clin Investig 129:531\u2013545","journal-title":"J Clin Investig"},{"key":"182_CR51","doi-asserted-by":"publisher","first-page":"106ra107","DOI":"10.1126\/scitranslmed.3002847","volume":"3","author":"FG Osorio","year":"2011","unstructured":"Osorio FG, Navarro CL, Cadi\u00f1anos J, L\u00f3pez-Mej\u00eda IC, Quir\u00f3s PM, Bartoli C, Rivera J, Tazi J, Guzm\u00e1n G, Varela I et al (2011) Splicing-directed therapy in a new mouse model of human accelerated aging. Sci Transl Med 3:106ra107\u2013106ra101","journal-title":"Sci Transl Med"},{"key":"182_CR52","doi-asserted-by":"publisher","first-page":"2301","DOI":"10.1172\/JCI133661","volume":"130","author":"C Owen-Woods","year":"2020","unstructured":"Owen-Woods C, Joulia R, Barkaway A, Rolas L, Ma B, Nottebaum AF, Arkill KP, Stein M, Girbl T, Golding M et al (2020) Local microvascular leakage promotes trafficking of activated neutrophils to remote organs. J Clin Investig 130:2301\u20132318","journal-title":"J Clin Investig"},{"key":"182_CR53","doi-asserted-by":"publisher","first-page":"1259","DOI":"10.1038\/nm1196-1259","volume":"2","author":"M Perretti","year":"1996","unstructured":"Perretti M, Croxtall JD, Wheller SK, Goulding NJ, Hannon R, Flower RJ (1996) Mobilizing lipocortin 1 in adherent human leukocytes downregulates their transmigration. Nat Med 2:1259\u20131262","journal-title":"Nat Med"},{"key":"182_CR54","doi-asserted-by":"publisher","first-page":"1989","DOI":"10.1016\/j.immuni.2021.07.012","volume":"54","author":"N Reglero-Real","year":"2021","unstructured":"Reglero-Real N, P\u00e9rez-Guti\u00e9rrez L, Yoshimura A, Rolas L, Garrido-Mesa J, Barkaway A, Pickworth C, Saleeb RS, Gonzalez-Nu\u00f1ez M, Austin-Williams SN et al (2021) Autophagy modulates endothelial junctions to restrain neutrophil diapedesis during inflammation. Immunity 54:1989\u20132004.e1989","journal-title":"Immunity"},{"key":"182_CR55","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1111\/acel.12458","volume":"15","author":"CM Roos","year":"2016","unstructured":"Roos CM, Zhang B, Palmer AK, Ogrodnik MB, Pirtskhalava T, Thalji NM, Hagler M, Jurk D, Smith LA, Casaclang\u2010Verzosa G et al (2016) Chronic senolytic treatment alleviates established vasomotor dysfunction in aged or atherosclerotic mice. Aging Cell 15:973\u2013977","journal-title":"Aging Cell"},{"key":"182_CR56","doi-asserted-by":"publisher","first-page":"1777","DOI":"10.1161\/CIRCULATIONAHA.121.055313","volume":"144","author":"A S\u00e1nchez-L\u00f3pez","year":"2021","unstructured":"S\u00e1nchez-L\u00f3pez A, Espin\u00f3s-Est\u00e9vez C, Gonz\u00e1lez-G\u00f3mez C, Gonzalo P, Andr\u00e9s-Manzano MJ, Fanjul V, Riquelme-Borja R, Hamczyk MR, Mac\u00edas \u00c1, Del Campo L et al (2021) Cardiovascular progerin suppression and lamin A restoration rescue Hutchinson-Gilford progeria syndrome. Circulation 144:1777\u20131794","journal-title":"Circulation"},{"key":"182_CR57","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1038\/s41591-018-0338-6","volume":"25","author":"O Santiago-Fern\u00e1ndez","year":"2019","unstructured":"Santiago-Fern\u00e1ndez O, Osorio FG, Quesada V, Rodr\u00edguez F, Basso S, Maeso D, Rolas L, Barkaway A, Nourshargh S, Folgueras AR et al (2019) Development of a CRISPR\/Cas9-based therapy for Hutchinson\u2013Gilford progeria syndrome. Nat Med 25:423\u2013426","journal-title":"Nat Med"},{"key":"182_CR58","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14532","volume":"8","author":"MJ Schafer","year":"2017","unstructured":"Schafer MJ, White TA, Iijima K, Haak AJ, Ligresti G, Atkinson EJ, Oberg AL, Birch J, Salmonowicz H, Zhu Y et al (2017) Cellular senescence mediates fibrotic pulmonary disease. Nat Commun 8:14532","journal-title":"Nat Commun"},{"key":"182_CR59","doi-asserted-by":"publisher","first-page":"6829","DOI":"10.18632\/aging.204248","volume":"14","author":"T Schmauck-Medina","year":"2022","unstructured":"Schmauck-Medina T, Moli\u00e8re A, Lautrup S, Zhang J, Chlopicki S, Madsen HB, Cao S, Soendenbroe C, Mansell E, Vestergaard MB et al (2022) New hallmarks of ageing: a 2022 Copenhagen ageing meeting summary. Aging 14:6829\u20136839","journal-title":"Aging"},{"key":"182_CR60","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1038\/s41586-021-03307-7","volume":"592","author":"B Schumacher","year":"2021","unstructured":"Schumacher B, Pothof J, Vijg J, Hoeijmakers JHJ (2021) The central role of DNA damage in the ageing process. Nature 592:695\u2013703","journal-title":"Nature"},{"key":"182_CR61","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1038\/s41569-019-0326-7","volume":"17","author":"C Silvestre-Roig","year":"2020","unstructured":"Silvestre-Roig C, Braster Q, Ortega-Gomez A, Soehnlein O (2020) Neutrophils as regulators of cardiovascular inflammation. Nat Rev Cardiol 17:327\u2013340","journal-title":"Nat Rev Cardiol"},{"key":"182_CR62","doi-asserted-by":"publisher","first-page":"e00653","DOI":"10.1128\/IAI.00653-20","volume":"89","author":"SR Simmons","year":"2021","unstructured":"Simmons SR, Bhalla M, Herring SE, Tchalla EYI, Bou Ghanem EN (2021) Older but not wiser: the age-driven changes in neutrophil responses during pulmonary infections. Infect Immun 89:e00653\u201300620","journal-title":"Infect Immun"},{"key":"182_CR63","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1038\/s43587-021-00151-2","volume":"1","author":"M Suda","year":"2021","unstructured":"Suda M, Shimizu I, Katsuumi G, Yoshida Y, Hayashi Y, Ikegami R, Matsumoto N, Yoshida Y, Mikawa R, Katayama A et al (2021) Senolytic vaccination improves normal and pathological age-related phenotypes and increases lifespan in progeroid mice. Nat aging 1:1117\u20131126","journal-title":"Nat aging"},{"key":"182_CR64","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aay5556","volume":"6","author":"S Sun","year":"2020","unstructured":"Sun S, Qin W, Tang X, Meng Y, Hu W, Zhang S, Qian M, Liu Z, Cao X, Pang Q et al (2020) Vascular endothelium\u2013targeted Sirt7 gene therapy rejuvenates blood vessels and extends life span in a Hutchinson-Gilford progeria model. Sci Adv 6:eaay5556","journal-title":"Sci Adv"},{"key":"182_CR65","doi-asserted-by":"publisher","first-page":"966","DOI":"10.1172\/JCI64098","volume":"123","author":"T Tchkonia","year":"2013","unstructured":"Tchkonia T, Zhu Y, Van Deursen J, Campisi J, Kirkland JL (2013) Cellular senescence and the senescent secretory phenotype: therapeutic opportunities. J Clin Investig 123:966\u2013972","journal-title":"J Clin Investig"},{"key":"182_CR66","doi-asserted-by":"publisher","first-page":"508","DOI":"10.3389\/fimmu.2014.00508","volume":"5","author":"C Tecchio","year":"2014","unstructured":"Tecchio C, Micheletti A, Cassatella MA (2014) Neutrophil-derived cytokines: facts beyond expression. Front Immunol 5:508","journal-title":"Front Immunol"},{"key":"182_CR67","doi-asserted-by":"publisher","first-page":"R35","DOI":"10.1530\/VB-20-0013","volume":"3","author":"KK Ting","year":"2021","unstructured":"Ting KK, Coleman P, Zhao Y, Vadas MA, Gamble JR (2021) The aging endothelium. Vasc Biol 3:R35\u2013R47","journal-title":"Vasc Biol"},{"key":"182_CR68","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1111\/imr.13153","volume":"314","author":"K Van Avondt","year":"2023","unstructured":"Van Avondt K, Strecker JK, Tulotta C, Minnerup J, Schulz C, Soehnlein O (2023) Neutrophils in aging and aging\u2010related pathologies. Immunol Rev 314:357\u2013375","journal-title":"Immunol Rev"},{"key":"182_CR69","doi-asserted-by":"publisher","first-page":"1193","DOI":"10.1161\/ATVBAHA.109.187450","volume":"29","author":"MB Voisin","year":"2009","unstructured":"Voisin MB, Woodfin A, Nourshargh S (2009) Monocytes and neutrophils exhibit both distinct and common mechanisms in penetrating the vascular basement membrane in vivo. Arterioscler Thromb Vasc Biol 29:1193\u20131199","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"182_CR70","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1038\/ni.2062","volume":"12","author":"A Woodfin","year":"2011","unstructured":"Woodfin A, Voisin M-B, Beyrau M, Colom B, Caille D, Diapouli F-M, Nash GB, Chavakis T, Albelda SM, Rainger GE et al (2011) The junctional adhesion molecule JAM-C regulates polarized transendothelial migration of neutrophils in vivo. Nat Immunol 12:761\u2013769","journal-title":"Nat Immunol"},{"key":"182_CR71","doi-asserted-by":"publisher","first-page":"1246","DOI":"10.1038\/s41591-018-0092-9","volume":"24","author":"M Xu","year":"2018","unstructured":"Xu M, Pirtskhalava T, Farr JN, Weigand BM, Palmer AK, Weivoda MM, Inman CL, Ogrodnik MB, Hachfeld CM, Fraser DG et al (2018) Senolytics improve physical function and increase lifespan in old age. Nat Med 24:1246\u20131256","journal-title":"Nat Med"},{"key":"182_CR72","doi-asserted-by":"publisher","DOI":"10.1093\/ehjopen\/oeac047","volume":"2","author":"Q Xu","year":"2022","unstructured":"Xu Q, Mojiri A, Boulahouache L, Morales E, Walther BK, Cooke JP (2022) Vascular senescence in progeria: role of endothelial dysfunction. Eur Heart J Open 2:oeac047","journal-title":"Eur Heart J Open"}],"container-title":["EMBO Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1038\/s44319-024-00182-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1038\/s44319-024-00182-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1038\/s44319-024-00182-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T18:02:57Z","timestamp":1785780177000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1038\/s44319-024-00182-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,25]]},"references-count":72,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,9,10]]}},"alternative-id":["182"],"URL":"https:\/\/doi.org\/10.1038\/s44319-024-00182-x","relation":{},"ISSN":["1469-3178"],"issn-type":[{"value":"1469-3178","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,25]]},"assertion":[{"value":"31 October 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 May 2024","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 June 2024","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 June 2024","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Disclosure and competing interests statement"}}],"article-number":"10"}}