{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T11:21:07Z","timestamp":1789730467783,"version":"4.0.1"},"reference-count":81,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T00:00:00Z","timestamp":1760918400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T00:00:00Z","timestamp":1760918400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100002287","name":"Progeria Research Foundation","doi-asserted-by":"publisher","award":["2022\u201082"],"award-info":[{"award-number":["2022\u201082"]}],"id":[{"id":"10.13039\/100002287","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Hutchinson\u2010Gilford Progeria Syndrome (HGPS) is a fatal genetic disorder caused by progerin, a mutant lamin A variant that disrupts nuclear architecture and drives systemic cellular dysfunction. Gastrointestinal (GI) involvement in HGPS remains poorly understood, despite growing evidence of gut abnormalities and microbial dysbiosis in progeroid mouse models. Here, we provide the first comprehensive characterization of colonic pathology in\n                    <jats:italic>Lmna<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>G609G\/G609G<\/jats:italic>\n                    <\/jats:sup>\n                    mice and assess the therapeutic impact of baricitinib (Bar), a JAK\u2013STAT inhibitor, lonafarnib (FTI), the only FDA\u2010approved therapy, and their combination on colonic health. Bar + FTI combination therapy most effectively lowered progerin levels, preserved colonic architecture and epithelial regeneration markers, while also reducing inflammation, cellular senescence, and early fibrotic changes. Notably, FTI monotherapy aggravated inflammation via STAT1 activation, an effect reversed by Bar co\u2010administration. Bar also emerged as the primary driver in mitigating colonic tissue senescence, highlighting its role in supporting intestinal homeostasis. In addition, we observed marked microbial dysbiosis in HGPS mice, particularly in late\u2010stage disease. While both monotherapies induced distinct shifts in gut microbiota, combination therapy preserved a profile more closely resembling healthy controls. These findings expand the current understanding of GI involvement in HGPS and identify the colon as a site where JAK\u2013STAT inhibition enhances the therapeutic profile of FTI.\n                  <\/jats:p>","DOI":"10.1111\/acel.70273","type":"journal-article","created":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T14:53:47Z","timestamp":1760972027000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Baricitinib Augments Lonafarnib Therapy to Preserve Colonic Homeostasis and Microbial Balance in a Mouse Model of Progeria"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-4865-0187","authenticated-orcid":false,"given":"Moritz","family":"Schroll","sequence":"first","affiliation":[{"name":"Epigenetics of Aging, Department of Dermatology and Allergy, TUM School of Medicine and Health, Munich Institute of Biomedical Engineering Technical University of Munich  Garching Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yacine","family":"Amar","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergy, School of Medicine Technical University of Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0461-0645","authenticated-orcid":false,"given":"Peter","family":"Kr\u00fcger","sequence":"additional","affiliation":[{"name":"Epigenetics of Aging, Department of Dermatology and Allergy, TUM School of Medicine and Health, Munich Institute of Biomedical Engineering Technical University of Munich  Garching Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6020-2814","authenticated-orcid":false,"given":"Klaus","family":"Neuhaus","sequence":"additional","affiliation":[{"name":"Core Facility Microbiome, ZIEL\u2010Institute for Food &amp; Health Technical University of Munich  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 Technical University of Munich  Garching Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12867\u2010017\u20100084\u20101"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40168\u2010021\u201001067\u20100"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22147474"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.07.089"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010019\u20100504\u20105"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9051201"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.59368\/agingbio.20230009"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI43578"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506001102"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010022\u201005168\u2010y"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276\u2010024\u201001179\u20101"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00018.2018"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1084125"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587\u2010020\u20100548\u20106"},{"key":"e_1_2_9_16_1","unstructured":"Eiger BioPharmaceuticals Inc.2020.\u201cZOKINVYTM (Lonafarnib) Capsules for Oral Use [US Prescribing Information].\u201dhttps:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2020\/213969s000lbl.pdf."},{"key":"e_1_2_9_17_1","unstructured":"Eli Lilly and Company.2022.\u201cOLUMIANT (Baricitinib) Tablets for Oral Use.\u201dhttps:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2022\/207924s006lbl.pdf."},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01629"},{"key":"e_1_2_9_19_1","unstructured":"European Medicines Agency.2023.\u201cOlumiant 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A Guide for Families & Health Care Providers of Children With Progeria.\u201dhttps:\/\/www.progeriaresearch.org\/wp\u2010content\/uploads\/2022\/03\/English\u2010Progeria\u2010Handbook\u2010Edition\u20102.pdf."},{"key":"e_1_2_9_53_1","unstructured":"Progeria Research Foundation.2024.\u201cPRF by the 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Food and Drug Administration.2020.\u201cFDA Approves First Treatment for Hutchinson\u2010Gilford Progeria Syndrome and Some Progeroid Laminopathies.\u201dhttps:\/\/www.fda.gov\/news\u2010events\/press\u2010announcements\/fda\u2010approves\u2010first\u2010treatment\u2010hutchinson\u2010gilford\u2010progeria\u2010syndrome\u2010and\u2010some\u2010progeroid\u2010laminopathies."},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1161\/atvbaha.117.309451"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1019532108"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.14188"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1128\/Aem.00062\u201007"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10787\u2010023\u201001396\u20106"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1515386112"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2019.110784"},{"key":"e_1_2_9_79_1","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2016.75"},{"key":"e_1_2_9_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2023.111841"},{"key":"e_1_2_9_81_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587\u2010023\u201000361\u2010w"},{"key":"e_1_2_9_82_1","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms11102580"}],"container-title":["Aging 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