{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:06:15Z","timestamp":1790690775402,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Age\u2010related hearing loss (ARHL) is a prevalent sensory disorder in the elderly, yet the molecular mechanisms underlying cochlear aging remain incompletely understood. While insulin\u2010like growth factor 1 (IGF\u20101) has been implicated in ARHL, its role in the stria vascularis, particularly in pericyte\u2010mediated blood\u2010labyrinth barrier (BLB) regulation, is poorly defined. We performed transcriptomic analysis of FACS\u2010purified pericytes from young and aged mouse stria vascularis. Functional studies were conducted using primary pericyte cultures, lentiviral gene modulation, and AAV\u2010mediated in\u00a0vivo delivery. Auditory function was assessed by auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE). Molecular changes were evaluated via qPCR, western blot, immunofluorescence, flow cytometry, and transmission electron microscopy (TEM). Transcriptomics revealed significant downregulation of\n                    <jats:italic>Igf1<\/jats:italic>\n                    and\n                    <jats:italic>Slc25a33<\/jats:italic>\n                    in aged pericytes, with enrichment of the TGF\u2010\u03b2 signaling pathway. IGF\u20101 deficiency suppressed SLC25A33 expression in\u00a0vitro, leading to mitochondrial ROS (mtROS) accumulation, activation of TGF\u2010\u03b2\/Smad2 signaling, and pericyte phenotypic switching, characterized by increased \u03b1\u2010SMA and decreased E\u2010cadherin. In\u00a0vivo, suppression of IGF\u20101 or SLC25A33 activated TGF\u2010\u03b2\/Smad2 signaling in the stria vascularis, disrupted BLB ultrastructure, and exacerbated hearing loss. Conversely, exogenous IGF\u20101 or SLC25A33 overexpression attenuated these effects and partially restored auditory function. Our findings identify a novel IGF\u20101\/SLC25A33\u2013TGF\u2010\u03b2\/Smad2 axis that regulates pericyte activation and BLB integrity in the aging cochlea. This pathway provides mechanistic insight into ARHL pathogenesis and highlights a potential therapeutic target for preserving hearing in older adults.\n                  <\/jats:p>","DOI":"10.1111\/acel.70712","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:15:50Z","timestamp":1790687750000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>IGF<\/scp>\n                    \u20101\/\n                    <scp>SLC25A33<\/scp>\n                    Maintains Blood\u2010Labyrinth Barrier Integrity by Suppressing\n                    <scp>TGF<\/scp>\n                    \u2010\u03b2\/Smad2\u2010Mediated Pericyte Activation in Age\u2010Related Hearing Loss"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-9816-1246","authenticated-orcid":false,"given":"Rui","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Otolaryngology, The First Affiliated Hospital Army Medical University  Chongqing China"},{"name":"Department of Neurology, The Second Affiliated Hospital Army Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, The First Affiliated Hospital Army Medical University  Chongqing China"},{"name":"Department of Cell Biology Army Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, The First Affiliated Hospital Army Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, The First Affiliated Hospital Army Medical University  Chongqing 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Deficiency and Hearing Loss: Molecular Clues and Clinical Implications","volume":"10","author":"Varela\u2010Nieto I.","year":"2013","journal-title":"Pediatric Endocrinology Reviews"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.01404"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4413"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.143285"}],"container-title":["Aging 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