{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T03:49:39Z","timestamp":1790221779022,"version":"4.1.0"},"reference-count":80,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T00:00:00Z","timestamp":1747612800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100002287","name":"Fondazione IRCCS Istituto Neurologico","doi-asserted-by":"publisher","award":["PRF 2022-82"],"award-info":[{"award-number":["PRF 2022-82"]}],"id":[{"id":"10.13039\/100002287","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002287","name":"Fondazione IRCCS Istituto Neurologico","doi-asserted-by":"publisher","award":["EJPRD19-206"],"award-info":[{"award-number":["EJPRD19-206"]}],"id":[{"id":"10.13039\/100002287","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002287","name":"Fondazione IRCCS Istituto Neurologico","doi-asserted-by":"publisher","award":["01KX1012"],"award-info":[{"award-number":["01KX1012"]}],"id":[{"id":"10.13039\/100002287","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002287","name":"Fondazione IRCCS Istituto Neurologico","doi-asserted-by":"publisher","award":["PRF 2022-82"],"award-info":[{"award-number":["PRF 2022-82"]}],"id":[{"id":"10.13039\/100002287","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fondazione Regionale per la Ricerca Biomedica (Regione Lombardia)","award":["PRF 2022-82"],"award-info":[{"award-number":["PRF 2022-82"]}]},{"name":"Fondazione Regionale per la Ricerca Biomedica (Regione Lombardia)","award":["EJPRD19-206"],"award-info":[{"award-number":["EJPRD19-206"]}]},{"name":"Fondazione Regionale per la Ricerca Biomedica (Regione Lombardia)","award":["01KX1012"],"award-info":[{"award-number":["01KX1012"]}]},{"name":"Fondazione Regionale per la Ricerca Biomedica (Regione Lombardia)","award":["PRF 2022-82"],"award-info":[{"award-number":["PRF 2022-82"]}]},{"name":"German Federal Ministry of Education and Research","award":["PRF 2022-82"],"award-info":[{"award-number":["PRF 2022-82"]}]},{"name":"German Federal Ministry of Education and Research","award":["EJPRD19-206"],"award-info":[{"award-number":["EJPRD19-206"]}]},{"name":"German Federal Ministry of Education and Research","award":["01KX1012"],"award-info":[{"award-number":["01KX1012"]}]},{"name":"German Federal Ministry of Education and Research","award":["PRF 2022-82"],"award-info":[{"award-number":["PRF 2022-82"]}]},{"name":"German Center for Diabetes Research (DZD)","award":["PRF 2022-82"],"award-info":[{"award-number":["PRF 2022-82"]}]},{"name":"German Center for Diabetes Research (DZD)","award":["EJPRD19-206"],"award-info":[{"award-number":["EJPRD19-206"]}]},{"name":"German Center for Diabetes Research (DZD)","award":["01KX1012"],"award-info":[{"award-number":["01KX1012"]}]},{"name":"German Center for Diabetes Research (DZD)","award":["PRF 2022-82"],"award-info":[{"award-number":["PRF 2022-82"]}]},{"DOI":"10.13039\/100002287","name":"Progeria Research Foundation","doi-asserted-by":"publisher","award":["PRF 2022-82"],"award-info":[{"award-number":["PRF 2022-82"]}],"id":[{"id":"10.13039\/100002287","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002287","name":"Progeria Research Foundation","doi-asserted-by":"publisher","award":["EJPRD19-206"],"award-info":[{"award-number":["EJPRD19-206"]}],"id":[{"id":"10.13039\/100002287","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002287","name":"Progeria Research Foundation","doi-asserted-by":"publisher","award":["01KX1012"],"award-info":[{"award-number":["01KX1012"]}],"id":[{"id":"10.13039\/100002287","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002287","name":"Progeria Research Foundation","doi-asserted-by":"publisher","award":["PRF 2022-82"],"award-info":[{"award-number":["PRF 2022-82"]}],"id":[{"id":"10.13039\/100002287","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hutchinson\u2013Gilford progeria syndrome (HGPS) is a rare, fatal, and premature aging disorder caused by progerin, a truncated form of lamin A that disrupts nuclear architecture, induces systemic inflammation, and accelerates senescence. While the farnesyltransferase inhibitor lonafarnib extends the lifespan by limiting progerin farnesylation, it does not address the chronic inflammation or the senescence-associated secretory phenotype (SASP), which worsens disease progression. In this study, we investigated the combined effects of baricitinib (BAR), a JAK1\/2 inhibitor, and lonafarnib (FTI) in a LmnaG609G\/G609G mouse model of HGPS. BAR + FTI therapy synergistically extended the lifespan by 25%, surpassing the effects of either monotherapy. Treated mice showed improved health, as evidenced by reduced kyphosis, better fur quality, decreased incidence of cataracts, and less severe dysgnathia. Histological analyses indicated reduced fibrosis in the dermal, hepatic, and muscular tissues, restored cellularity and thickness in the aortic media, and improved muscle fiber integrity. Mechanistically, BAR decreased the SASP and inflammatory markers (e.g., IL-6 and PAI-1), complementing the progerin-targeting effects of FTI. This preclinical study demonstrates the synergistic potential of BAR + FTI therapy in addressing HGPS systemic and tissue-specific pathologies, offering a promising strategy for enhancing both lifespan and health.<\/jats:p>","DOI":"10.3390\/ijms26104849","type":"journal-article","created":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T07:34:03Z","timestamp":1747640043000},"page":"4849","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Baricitinib and Lonafarnib Synergistically Target Progerin and Inflammation, Improving Lifespan and Health in Progeria Mice"],"prefix":"10.3390","volume":"26","author":[{"given":"Peter","family":"Kr\u00fcger","sequence":"first","affiliation":[{"name":"Epigenetics of Aging, Department of Dermatology and Allergy, TUM School of Medicine and Health, Munich Institute of Biomedical Engineering (MIBE), Technical University of Munich (TUM), 85748 Garching, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4865-0187","authenticated-orcid":false,"given":"Moritz","family":"Schroll","sequence":"additional","affiliation":[{"name":"Epigenetics of Aging, Department of Dermatology and Allergy, TUM School of Medicine and Health, Munich Institute of Biomedical Engineering (MIBE), Technical University of Munich (TUM), 85748 Garching, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7762-5243","authenticated-orcid":false,"given":"Felix Quirin","family":"Fenzl","sequence":"additional","affiliation":[{"name":"Epigenetics of Aging, Department of Dermatology and Allergy, TUM School of Medicine and Health, Munich Institute of Biomedical Engineering (MIBE), Technical University of Munich (TUM), 85748 Garching, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramona","family":"Hartinger","sequence":"additional","affiliation":[{"name":"Epigenetics of Aging, Department of Dermatology and Allergy, TUM School of Medicine and Health, Munich Institute of Biomedical Engineering (MIBE), Technical University of Munich (TUM), 85748 Garching, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1220-1040","authenticated-orcid":false,"given":"Eva-Maria","family":"Lederer","sequence":"additional","affiliation":[{"name":"Epigenetics of Aging, Department of Dermatology and Allergy, TUM School of Medicine and Health, Munich Institute of Biomedical Engineering (MIBE), Technical University of Munich (TUM), 85748 Garching, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnes","family":"G\u00f6rlach","sequence":"additional","affiliation":[{"name":"Experimental and Molecular Pediatric Cardiology, Department of Pediatric Cardiology and Congenital Heart Diseases, German Heart Center Munich, Technical University Hospital, TUM School of Medicine and Health, 80636 Munich, Germany"},{"name":"German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, 80636 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie B.","family":"Gordon","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"},{"name":"Department of Pediatrics, Hasbro Children\u2019s Hospital, Warren Alpert Medical School of Brown University, Providence, RI 02912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1497-1524","authenticated-orcid":false,"given":"Paola","family":"Cavalcante","sequence":"additional","affiliation":[{"name":"Neurology 4-Neuroimmunology and Neuromuscular Diseases, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1032-9120","authenticated-orcid":false,"given":"Nicola","family":"Iacomino","sequence":"additional","affiliation":[{"name":"Neurology 4-Neuroimmunology and Neuromuscular Diseases, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgit","family":"Rathkolb","sequence":"additional","affiliation":[{"name":"Institute of Experimental Genetics, German Mouse Clinic, Helmholtz Center Munich (GmbH), German Research Center for Environmental Health, 85764 Neuherberg, Germany"},{"name":"Institute of Molecular Animal Breeding and Biotechnology, Gene Center, Ludwig Maximilian University of Munich, 81377 Munich, Germany"},{"name":"German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Antonio Aguilar","family":"Pimentel","sequence":"additional","affiliation":[{"name":"Institute of Experimental Genetics, German Mouse Clinic, Helmholtz Center Munich (GmbH), German Research Center for Environmental Health, 85764 Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"\u00d6stereicher","sequence":"additional","affiliation":[{"name":"Institute of Experimental Genetics, German Mouse Clinic, Helmholtz Center Munich (GmbH), German Research Center for Environmental Health, 85764 Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Spielmann","sequence":"additional","affiliation":[{"name":"Institute of Experimental Genetics, German Mouse Clinic, Helmholtz Center Munich (GmbH), German Research Center for Environmental Health, 85764 Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4701-5843","authenticated-orcid":false,"given":"Cordula Maria","family":"Wolf","sequence":"additional","affiliation":[{"name":"Experimental and Molecular Pediatric Cardiology, Department of Pediatric Cardiology and Congenital Heart Diseases, German Heart Center Munich, Technical University Hospital, TUM School of Medicine and Health, 80636 Munich, Germany"},{"name":"German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, 80636 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7898-2353","authenticated-orcid":false,"given":"Martin Hrabe","family":"de Angelis","sequence":"additional","affiliation":[{"name":"Institute of Experimental Genetics, German Mouse Clinic, Helmholtz Center Munich (GmbH), German Research Center for Environmental Health, 85764 Neuherberg, Germany"},{"name":"German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany"},{"name":"Experimental Genetics, TUM School of Life Sciences, Technical University of Munich, 85354 Freising, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4067-4977","authenticated-orcid":false,"given":"Karima","family":"Djabali","sequence":"additional","affiliation":[{"name":"Epigenetics of Aging, Department of Dermatology and Allergy, TUM School of Medicine and Health, Munich Institute of Biomedical Engineering (MIBE), Technical University of Munich (TUM), 85748 Garching, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1056\/NEJMoa0706898","article-title":"Phenotype and course of Hutchinson-Gilford progeria syndrome","volume":"358","author":"Merideth","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.cell.2013.12.028","article-title":"Progeria: A paradigm for translational medicine","volume":"156","author":"Gordon","year":"2014","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1542\/peds.2007-1356","article-title":"New approaches to progeria","volume":"120","author":"Kieran","year":"2007","journal-title":"Pediatrics"},{"key":"ref_4","unstructured":"Adam, M.P., Feldman, J., Mirzaa, G.M., Pagon, R.A., Wallace, S.E., and Amemiya, A. (2003). Hutchinson-Gilford Progeria Syndrome. GeneReviews\u00ae, University of Washington. Updated 19 October 2023."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/nature01629","article-title":"Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome","volume":"423","author":"Eriksson","year":"2003","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2055","DOI":"10.1126\/science.1084125","article-title":"Lamin A truncation in Hutchinson-Gilford progeria","volume":"300","author":"Bernard","year":"2003","journal-title":"Science"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/1742-4933-6-4","article-title":"Molecular ageing in progeroid syndromes: Hutchinson-Gilford progeria syndrome as a model","volume":"20","author":"Coutinho","year":"2009","journal-title":"Immu. Ageing"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"8963","DOI":"10.1073\/pnas.0402943101","article-title":"Accumulation of mutant lamin A causes progressive changes in nuclear architecture in Hutchinson-Gilford progeria syndrome","volume":"101","author":"Goldman","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1111\/acel.12070","article-title":"Hutchinson\u2013Gilford progeria syndrome through the lens of transcription","volume":"12","author":"Prokocimer","year":"2013","journal-title":"Aging Cell"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2605","DOI":"10.1242\/jcs.067306","article-title":"Role of progerin-induced telomere dysfunction in HGPS premature cellular senescence","volume":"123","author":"Beson","year":"2010","journal-title":"J. Cell Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.arr.2016.06.007","article-title":"Hutchinson-Gilford Progeria Syndrome: A premature aging disease caused by LMNA gene mutations","volume":"33","author":"Gonzalo","year":"2017","journal-title":"Ageing Res. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1111\/acel.12434","article-title":"Methylene blue alleviates nuclear and mitochondrial abnormalities in progeria","volume":"15","author":"Xiong","year":"2016","journal-title":"Aging Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"16321","DOI":"10.1016\/S0021-9258(19)85424-8","article-title":"Structural organization of the human gene encoding nuclear lamin A and nuclear lamin C","volume":"268","author":"Lin","year":"1993","journal-title":"J. Biol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4007","DOI":"10.1002\/j.1460-2075.1989.tb08583.x","article-title":"Modification of nuclear lamin proteins by a mevalonic acid derivative occurs in reticulocyte lysates and requires the cysteine residue of the C-terminal CXXM motif","volume":"8","author":"Vorburger","year":"1989","journal-title":"EMBO J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/0014-5793(89)81584-4","article-title":"Maturation of nuclear lamin A involves a specific carboxy-terminal trimming, which removes the polyisoprenylation site from the precursor; implications for the structure of the nuclear lamina","volume":"257","author":"Weber","year":"1989","journal-title":"FEBS Lett."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2215","DOI":"10.1242\/jcs.107.8.2215","article-title":"Expression of prelamin A but not mature lamin A confers sensitivity of DNA biosynthesis to Iovastatin on F9 teratocarcinoma cells","volume":"107","author":"Sinensky","year":"1994","journal-title":"J. Cell Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2959","DOI":"10.1093\/hmg\/ddi326","article-title":"Incomplete processing of mutant lamin A in Hutchinson-Gilford progeria leads to nuclear abnormalities, which are reversed by farnesyltransferase inhibition","volume":"14","author":"Glynn","year":"2005","journal-title":"Hum. Mol. Genet"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1126\/science.1124875","article-title":"A protein farnesyltransferase inhibitor ameliorates disease in a mouse model of progeria","volume":"311","author":"Fong","year":"2006","journal-title":"Science"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"14416","DOI":"10.1073\/pnas.0503712102","article-title":"Inhibiting farnesylation reverses the nuclear morphology defect in a HeLa cell model for Hutchinson-Gilford progeria syndrome","volume":"102","author":"Mallampalli","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"12879","DOI":"10.1073\/pnas.0506001102","article-title":"Inhibiting farnesylation of progerin prevents the characteristic nuclear blebbing of Hutchinson-Gilford progeria syndrome","volume":"102","author":"Capell","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1007\/s40265-020-01464-z","article-title":"Lonafarnib: First Approval","volume":"81","author":"Dhillon","year":"2021","journal-title":"Drugs"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"16666","DOI":"10.1073\/pnas.1202529109","article-title":"Clinical trial of a farnesyltransferase inhibitor in children with Hutchinson-Gilford progeria syndrome","volume":"109","author":"Gordon","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"M\u00e9gnin-Chanet, F., Lavelle, F., and Favaudon, V. (2002). The farnesyl transferase inhibitor RPR-130401 does not alter radiation susceptibility in human tumor cells with a K-Ras mutation in spite of large changes in ploidy and lamin B distribution. BMC Pharmacol., 2.","DOI":"10.1186\/1471-2210-2-2"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"142","DOI":"10.4161\/nucl.24089","article-title":"Disruption of lamin B1 and lamin B2 processing and localization by farnesyltransferase inhibitors","volume":"4","author":"Adam","year":"2013","journal-title":"Nucleus"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4997","DOI":"10.1073\/pnas.1019532108","article-title":"Protein farnesylation inhibitors cause donut-shaped cell nuclei attributable to a centrosome separation defect","volume":"108","author":"Verstraeten","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"24700","DOI":"10.18632\/oncotarget.8267","article-title":"Progerin impairs chromosome maintenance by depleting CENP-F from metaphase kinetochores in Hutchinson-Gilford progeria fibroblasts","volume":"7","author":"Eisch","year":"2016","journal-title":"Oncotarget"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Arnold, R., Vehns, E., Randl, H., and Djabali, K. (2021). Baricitinib, a JAK-STAT Inhibitor, Reduces the Cellular Toxicity of the Farnesyltransferase Inhibitor Lonafarnib in Progeria Cells. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22147474"},{"key":"ref_28","first-page":"255","article-title":"Genomic instability and innate immune responses to self-DNA in progeria","volume":"41","author":"Gonzalo","year":"2019","journal-title":"Gerontology"},{"key":"ref_29","first-page":"1287","article-title":"The cGAS-cGAMP-STING pathway connects DNA damage to inflammation, senescence, and cancer","volume":"215","author":"Li","year":"2018","journal-title":"JAMA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.molcel.2014.03.040","article-title":"The cGAS-cGAMP-STING pathway of cytosolic DNA sensing and signaling","volume":"54","author":"Cai","year":"2014","journal-title":"Mol. Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5504","DOI":"10.1111\/febs.15640","article-title":"Molecular and spatial mechanisms governing STING signalling","volume":"288","author":"Balka","year":"2021","journal-title":"FEBS J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"E6301","DOI":"10.1073\/pnas.1515386112","article-title":"JAK inhibition alleviates the cellular senescence-associated secretory phenotype and frailty in old age","volume":"112","author":"Xu","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4351","DOI":"10.2174\/1381612823666170714143426","article-title":"Application of Kinase Inhibitors for Anti-aging Intervention","volume":"23","author":"Cano","year":"2017","journal-title":"Curr. Pharm. Des."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/nature24050","article-title":"Cytoplasmic chromatin triggers inflammation in senescence and cancer","volume":"550","author":"Dou","year":"2017","journal-title":"Nature"},{"key":"ref_35","first-page":"1061","article-title":"Innate immune sensing of cytosolic chromatin fragments through cGAS promotes senescence","volume":"9","author":"Guey","year":"2017","journal-title":"Nat. Cell Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"E4612","DOI":"10.1073\/pnas.1705499114","article-title":"cGAS is essential for cellular senescence","volume":"114","author":"Yang","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.cell.2020.12.029","article-title":"Farnesyltransferase inhibition in HGPS","volume":"184","author":"Misteli","year":"2021","journal-title":"Cell"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/0968-0004(90)90213-U","article-title":"Prenyl proteins in eukaryotic cells: A new type of membrane anchor","volume":"15","author":"Glomset","year":"1990","journal-title":"Trends Biochem. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1038\/nrm.2015.11","article-title":"Protein prenylation: Unique fats make their mark on biology","volume":"17","author":"Wang","year":"2016","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_40","first-page":"109","article-title":"Immunology of Aging: The Birth of Inflammaging","volume":"64","author":"Fulop","year":"2023","journal-title":"Clin. Lab. Med."},{"key":"ref_41","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_42","doi-asserted-by":"crossref","unstructured":"Rea, I.M., Gibson, D.S., McGilligan, V., McNerlan, S.E., Alexander, H.D., and Ross, O.A. (2018). Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.00586"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1242\/jcs.00963","article-title":"The JAK\/STAT signaling pathway","volume":"117","author":"Rawlings","year":"2004","journal-title":"J. Cell Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e106210","DOI":"10.1016\/j.intimp.2020.106210","article-title":"The role of JAK\/STAT signaling pathway and its inhibitors in diseases","volume":"80","author":"Xin","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Sarapultsev, A., Gusev, E., Komelkova, M., Utepova, I., Luo, S., and Hu, D. (2023). JAK-STAT signaling in inflammation and stress-related diseases: Implications for therapeutic interventions. Mol. Biomed., 4.","DOI":"10.1186\/s43556-023-00151-1"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1007\/s40265-017-0856-4","article-title":"Baricitinib: A Review in Rheumatoid Arthritis","volume":"78","author":"Scott","year":"2018","journal-title":"Drugs"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Liu, C., Arnold, R., Henriques, G., and Djabali, K. (2019). Inhibition of JAK-STAT Signaling with Baricitinib Reduces Inflammation and Improves Cellular Homeostasis in Progeria Cells. Cells, 8.","DOI":"10.3390\/cells8101276"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"106ra107","DOI":"10.1126\/scitranslmed.3002847","article-title":"Splicing-directed therapy in a new mouse model of human accelerated aging","volume":"3","author":"Osorio","year":"2011","journal-title":"Sci. Transl. Med."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Kr\u00fcger, P., Schroll, M., Fenzl, F., Lederer, E.M., Hartinger, R., Arnold, R., Cagla Togan, D., Guo, R., Liu, S., and Petry, A. (2024). Inflammation and Fibrosis in Progeria: Organ-Specific Responses in an HGPS Mouse Model. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25179323"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e1240104","DOI":"10.1126\/science.1240104","article-title":"Nuclear Lamin-A Scales with Tissue Stiffness and Enhances Matrix-Directed Differentiation","volume":"341","author":"Swift","year":"2013","journal-title":"Science"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1002\/path.2999","article-title":"Nuclear lamins and laminopathies","volume":"226","author":"Worman","year":"2012","journal-title":"J. Pathol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1080\/19491034.2019.1589359","article-title":"Vascular smooth muscle cell loss underpins the accelerated atherosclerosis in Hutchinson-Gilford progeria syndrome","volume":"10","author":"Hamczyk","year":"2019","journal-title":"Nucleus"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Benedicto, I., Dorado, B., and Andr\u00e9s, V. (2021). Molecular and Cellular Mechanisms Driving Cardiovascular Disease in Hutchinson-Gilford Progeria Syndrome: Lessons Learned from Animal Models. Cells, 10.","DOI":"10.3390\/cells10051157"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.semcdb.2017.11.005","article-title":"Nuclear positioning in skeletal muscle","volume":"82","author":"Roman","year":"2018","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e13090","DOI":"10.1111\/acel.13090","article-title":"Progerin in muscle leads to thermogenic and metabolic defects via impaired calcium homeostasis","volume":"19","author":"Wang","year":"2020","journal-title":"Aging Cell"},{"key":"ref_56","unstructured":"European Medicines Agency (EMA) (2024, December 12). Zokinvy. Product Information. Available online: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/zokinvy."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1007\/s11357-022-00694-1","article-title":"Progerin induces a phenotypic switch in vascular smooth muscle cells and triggers replication stress and an aging-associated secretory signature","volume":"45","author":"Mahajan","year":"2023","journal-title":"GeroScience"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1161\/CIRCULATIONAHA.117.030856","article-title":"Vascular Smooth Muscle-Specific Progerin Expression Accelerates Atherosclerosis and Death in a Mouse Model of Hutchinson-Gilford Progeria Syndrome","volume":"138","author":"Hamczyk","year":"2018","journal-title":"Circulation"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2270345","DOI":"10.1080\/19491034.2023.2270345","article-title":"Prelamin A and ZMPSTE24 in premature and physiological aging","volume":"14","author":"Worman","year":"2023","journal-title":"Nucleus"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1161\/CIRCULATIONAHA.113.008285","article-title":"Impact of farnesylation inhibitors on survival in Hutchinson-Gilford progeria syndrome","volume":"130","author":"Gordon","year":"2014","journal-title":"Circulation"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e13285","DOI":"10.1111\/acel.13285","article-title":"Interleukin-6 neutralization ameliorates symptoms in prematurely aged mice","volume":"20","author":"Squarzoni","year":"2021","journal-title":"Aging Cell"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2006","DOI":"10.1016\/j.celrep.2018.01.090","article-title":"A Cell-Intrinsic Interferon-like Response Links Replication Stress to Cellular Aging Caused by Progerin","volume":"22","author":"Kreienkamp","year":"2018","journal-title":"Cell Rep."},{"key":"ref_63","first-page":"134","article-title":"NF-\u03baB signaling as a driver of ageing","volume":"326","author":"Osorio","year":"2016","journal-title":"Int. Rev. Cell Mol. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3068","DOI":"10.1038\/s41467-022-30800-y","article-title":"Transient expression of an adenine base editor corrects the Hutchinson-Gilford progeria syndrome mutation and improves the skin phenotype in mice","volume":"13","author":"Whisenant","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1038\/s41586-020-03086-7","article-title":"In vivo base editing rescues Hutchinson-Gilford progeria syndrome in mice","volume":"589","author":"Koblan","year":"2021","journal-title":"Nature"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1038\/s41434-023-00390-5","article-title":"Successes and challenges in clinical gene therapy","volume":"30","author":"Kohn","year":"2023","journal-title":"Gene Ther."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Kang, S.M., Yoon, M.H., Ahn, J., Kim, J.E., Kim, S.Y., Kang, S.Y., Joo, J., Park, S., Cho, J.H., and Woo, T.G. (2021). Progerinin, an optimized progerin-lamin A binding inhibitor, ameliorates premature senescence phenotypes of Hutchinson-Gilford progeria syndrome. Commun. Biol., 4.","DOI":"10.1038\/s42003-020-01540-w"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"e347","DOI":"10.1016\/S2665-9913(20)30032-1","article-title":"Safety profile of baricitinib for the treatment of rheumatoid arthritis over a median of 3 years of treatment: An updated integrated safety analysis","volume":"2","author":"Genovese","year":"2020","journal-title":"Lancet Rheumatol."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Lensing, M., and Jabbari, A. (2022). An overview of JAK\/STAT pathways and JAK inhibition in alopecia areata. Front. Immunol., 30.","DOI":"10.3389\/fimmu.2022.955035"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"101009","DOI":"10.1016\/j.molmet.2020.101009","article-title":"Baricitinib counteracts metaflammation, thus protecting against diet-induced metabolic abnormalities in mice","volume":"39","author":"Collotta","year":"2020","journal-title":"Mol. Metab."},{"key":"ref_71","unstructured":"Lilly, E. (2024, December 12). FDA Approves OLUMIANT\u00ae (Baricitinib) 2-mg Tablets for the Treatment of Adults with Moderately- to-Severely Active Rheumatoid Arthritis. Available online: https:\/\/investor.lilly.com\/node\/38996\/pdf."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1056\/NEJMoa1608345","article-title":"Baricitinib versus Placebo or Adalimumab in Rheumatoid Arthritis","volume":"376","author":"Taylor","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_73","unstructured":"Agency, E.M. (2024, December 12). Olumiant (Baricitinib)\u2014Medicine Overview. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/overview\/olumiant-epar-medicine-overview_en.pdf."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1016\/S0140-6736(23)00921-2","article-title":"Baricitinib in juvenile idiopathic arthritis: An international, phase 3, randomised, double-blind, placebo-controlled, withdrawal, efficacy, and safety trial","volume":"402","author":"Ramanan","year":"2023","journal-title":"Lancet"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1093\/bjd\/ljad096","article-title":"Efficacy and safety of baricitinib in combination with topical corticosteroids in paediatric patients with moderate-to-severe atopic dermatitis with an inadequate response to topical corticosteroids: Results from a phase III, randomized, double-blind, placebo-controlled study (BREEZE-AD PEDS)","volume":"189","author":"Torrelo","year":"2023","journal-title":"Br. J. Dermatol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"3209","DOI":"10.1007\/s13555-023-01063-2","article-title":"Clinical Benefits of Baricitinib Therapy According to Scalp Hair Regrowth in Patients with Severe Alopecia Areata","volume":"13","author":"Senna","year":"2023","journal-title":"Dermatol. Ther."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"110784","DOI":"10.1016\/j.exger.2019.110784","article-title":"Long term breeding of the Lmna G609G progeric mouse: Characterization of homozygous and heterozygous models","volume":"130","author":"Zaghini","year":"2019","journal-title":"Exp. Gerontol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1002\/9780470942390.mo130043","article-title":"Clinical Chemistry and Other Laboratory Tests on Mouse Plasma or Serum","volume":"3","author":"Rathkolb","year":"2013","journal-title":"Curr. Protoc. Mouse Biol."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Aguilar-Pimentel, J.A., Cho, Y.L., Gerlini, R., Calzada-Wack, J., Wimmer, M., Mayer-Kuckuk, P., Adler, T., Schmidt-Weber, C.B., Busch, D.H., and Fuchs, H. (2020). Increased estrogen to androgen ratio enhances immunoglobulin levels and impairs B cell function in male mice. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-75059-9"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/s44161-022-00018-8","article-title":"Extensive identification of genes involved in congenital and structural heart disorders and cardiomyopathy","volume":"1","author":"Spielmann","year":"2022","journal-title":"Nat. Cardiovasc. Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/10\/4849\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:35:04Z","timestamp":1760031304000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/10\/4849"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,19]]},"references-count":80,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["ijms26104849"],"URL":"https:\/\/doi.org\/10.3390\/ijms26104849","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,19]]}}}