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In this study, we systematically characterized the senescence landscape within the IBD microenvironment, with particular emphasis on fibroblast subpopulations and their systemic consequences. Single\u2010cell RNA sequencing (scRNA\u2010seq) dataset was applied to profile senescence\u2010associated feature heterogeneity. Fibroblasts were classified into high\u2010senescence (HS\u2010Fibro) and low\u2010senescence (LS\u2010Fibro) groups according to senescence scores. HS\u2010Fibro\u2010specific gene signatures were identified and functionally annotated. Intercellular communication networks were constructed using CellChat to delineate the HS\u2010Fibro interactome atlas, with emphasis on identifying cellular targets responsive to senescence\u2010associated secretory phenotype (SASP) signals. Integrated microarray datasets were employed to elucidate the systemic impact of HS\u2010Fibro in IBD. Through the integration of differential expression analysis, Weighted Gene Co\u2010expression Network Analysis (WGCNA), and an ensemble of 113 machine learning algorithms, seven hub genes implicated in IBD progression were systematically identified and prioritized. In the IBD microenvironment, fibroblasts exhibited enhanced senescence activity. HS\u2010Fibro displayed potent pro\u2010inflammatory properties and enhanced communicative capacity. IBD patients with high HS\u2010Fibro infiltration showed sustained immune\u2010inflammatory activity. Systematic bioinformatic analysis and immunohistochemistry validation identified ADAMTS2 as a robust diagnostic indicator for IBD, with substantially elevated expression in patients relative to controls. The human colon fibroblast cell line CCD\u201018Co was treated with H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    to establish a cellular senescence model, demonstrating marked upregulation of ADAMTS2, SASP markers, and fibrosis\u2010related genes. Moreover, siRNA\u2010mediated knockdown of ADAMTS2 resulted in obvious attenuation of these SASP and fibrosis\u2010associated genes.\n                  <\/jats:p>","DOI":"10.1096\/fj.202602171rr","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T07:09:32Z","timestamp":1790147372000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative Multi\u2010Omics and Machine Learning Reveal Senescent Fibroblast\u2010Associated\n                    <scp>ADAMTS2<\/scp>\n                    as a Critical Indicator of Intestinal Inflammation in\n                    <scp>IBD<\/scp>"],"prefix":"10.1096","volume":"40","author":[{"given":"Yueqi","family":"Liu","sequence":"first","affiliation":[{"name":"Precision Clinical Laboratory Central People's Hospital of Zhanjiang, Guangdong Medical University Zhanjiang Central Hospital  Zhanjiang 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