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It is currently not known whether the aging process affects the response to injury of cholangiocytes. The aim of this study was to identify molecular pathways associated with cholangiocyte aging and to determine their effects in the biological response to injury of biliary cells. A panel of microRNAs (miRs) involved in aging processes was evaluated in cholangiocytes of young and old mice (2 months and 22 months of age, respectively) and subjected to a model of sclerosing cholangitis. Intracellular pathways that are common to elevated miRs were identified by <jats:italic toggle=\"yes\">in silico<\/jats:italic> analysis. Cell proliferation and senescence were evaluated in Twinfilin\u20101 (<jats:italic toggle=\"yes\">Twf1<\/jats:italic>) knocked\u2010down cells. <jats:italic toggle=\"yes\">In vivo<\/jats:italic>, senescence\u2010accelerated prone mice (<jats:italic toggle=\"yes\">Samp8<\/jats:italic>, a model for accelerated aging), <jats:italic toggle=\"yes\">Twf1\u2010\/\u2010\n                           <\/jats:italic>, or their respective controls were subjected to DDC (3,5\u2010diethoxycarbonyl\u20101,4\u2010dihydrocollidine). Cholangiocytes from DDC\u2010treated mice showed up\u2010regulation of a panel of aging\u2010related<jats:italic toggle=\"yes\"> miRs<\/jats:italic>. <jats:italic toggle=\"yes\">Twf1 <\/jats:italic>was identified by <jats:italic toggle=\"yes\">in silico <\/jats:italic>analysis as a common target of the up\u2010regulated <jats:italic toggle=\"yes\">miRs<\/jats:italic>. <jats:italic toggle=\"yes\">Twf1<\/jats:italic> expression was increased both in aged and diseased cholangiocytes, and in human cholangiopathies. Knock\u2010down of <jats:italic toggle=\"yes\">Twf1<\/jats:italic> in cholangiocytes reduced cell proliferation. Senescence and senescence\u2010associated secretory phenotype marker expression increased in <jats:italic toggle=\"yes\">Twf1<\/jats:italic> knocked\u2010down cholangiocytes following pro\u2010proliferative and pro\u2010senescent (10\u2010day lipopolysaccharide) stimulation. <jats:italic toggle=\"yes\">In vivo<\/jats:italic>, <jats:italic toggle=\"yes\">Samp8<\/jats:italic> mice showed increased biliary proliferation, fibrosis, and <jats:italic toggle=\"yes\">Twf1<\/jats:italic> protein expression level, whereas <jats:italic toggle=\"yes\">Twf1\u2010\/\u2010\n                           <\/jats:italic> had a tendency toward lower biliary proliferation and fibrosis following DDC administration compared with control animals. <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic> We identified Twf1 as an important mediator of both cholangiocyte adaptation to aging processes and response to injury. Our data suggest that disease and aging might share common intracellular pathways.<\/jats:p>","DOI":"10.1002\/hep.30466","type":"journal-article","created":{"date-parts":[[2018,12,18]],"date-time":"2018-12-18T15:44:20Z","timestamp":1545147860000},"page":"883-898","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":13,"title":["Aging\u2010Related Expression of Twinfilin\u20101 Regulates Cholangiocyte Biological Response to Injury"],"prefix":"10.1097","volume":"70","author":[{"given":"Luca","family":"Maroni","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology,Universit\u00e0 Politecnica delle Marche,Ancona,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Pinto","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology,Universit\u00e0 Politecnica delle 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Sebastian,Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Spallacci","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology,Universit\u00e0 Politecnica delle Marche,Ancona,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Cristina","family":"Albertini","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Sciences,Universit\u00e0 degli Studi di Urbino \u201cCarlo Bo\u201d,Urbino,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiorenza","family":"Orlando","sequence":"additional","affiliation":[{"name":"Advanced Technology Center for Aging Research, Experimental Animal Models for Aging Unit,Scientific Technological Area, IRCCS INRCA,Ancona,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Provinciali","sequence":"additional","affiliation":[{"name":"Advanced Technology Center for Aging Research, 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