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Our study provided direct evidence from older human and mouse small intestines of the adverse impact of aging on Paneth cell functionality by impaired mitochondrial metabolism. Mechanistic investigation revealed a specific elevation of Paneth cell enriched microRNA\u2010152 (miR\u2010152) in aging small intestinal epithelium. Increased miR\u2010152 impaired Paneth cells of aging small intestine by inhibiting mitochondrial protein Prohibitin1 (PHB1) expression and disrupting mitochondrial respiration. Moreover, the levels of\n                    <jats:italic>circHIPK3<\/jats:italic>\n                    , an intestinal circular RNA that counters the function of miR\u2010152, also declined in older intestines, further enabling miR\u2010152\u2010mediated deterioration in Paneth cell function. Conversely, antagonizing miR\u2010152 improved mitochondrial metabolism by restoring PHB1 levels and ameliorated the functional decline of old Paneth cells. Our findings indicate that dysregulated miR\u2010152 expression and activity play a central role in the loss of Paneth cell homeostasis in the aging small intestine, offering translational insights for protecting intestinal mucosal integrity in older patients.\n                  <\/jats:p>","DOI":"10.1111\/acel.70542","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T12:20:28Z","timestamp":1778674828000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Age\u2010Associated Impairment of Paneth Cells Driven by\n                    <scp>microRNA<\/scp>\n                    \u2010152 Promotes Intestinal Epithelial Vulnerability to Pathological Stress"],"prefix":"10.1111","volume":"25","author":[{"given":"Bridgette","family":"Warner","sequence":"first","affiliation":[{"name":"Cell Biology Group, Department of Surgery University of Maryland School of Medicine  Baltimore Maryland USA"},{"name":"Veterans Affairs Maryland Healthcare System  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haonan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Cell Biology Group, Department of Surgery University of Maryland School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongxia","family":"Chen","sequence":"additional","affiliation":[{"name":"Cell Biology Group, Department of Surgery University of Maryland School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"VanderStoep","sequence":"additional","affiliation":[{"name":"Cell Biology Group, Department of Surgery University of Maryland School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana S. 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