{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:30:54Z","timestamp":1787502654171,"version":"build-2736575974"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T00:00:00Z","timestamp":1746144000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Senescent cells (SCs) accumulate with age and play a causative role in age-related diseases, such as idiopathic pulmonary fibrosis (IPF). Clearance of SCs attenuates lung fibrogenesis and favors fibrosis resolution, suggesting that targeting of SCs is recognized as a promising therapeutic approach for IPF. Isothiocyanates (ITCs) are natural compounds with anticancer and anti-aging properties, but their role in IPF remains unclear. The aim of our study to investigate whether benzyl isothiocyanate (BITC), a type of ITCs, can act as a senolytic agent thereby attenuating pulmonary fibrosis in aged mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Primary lung fibroblasts from IPF patients and controls were cultured and treated with various ITCs to identify potential senolytic agents. Senescence-associated \u03b2-galactosidase staining, Cell viability assays, Annexin V\/PI double staining, Caspase 3 activity assay, Western blot analysis, and qPCR were performed to evaluate senescence markers, cell viability, and apoptosis-related proteins after BITC treatment of senescent IPF lung fibroblasts\n                      <jats:italic>in vitro<\/jats:italic>\n                      . HE staining, Masson staining, Hydroxyproline assay, and Western blot analysis were used to assess the pathological progress, collagen content of lung tissues, and fibrotic gene expression changes after BITC treatment in C57BL\/6 aged mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Using senescent IPF fibroblasts, we screened and identified BITC as a potent senolytic drug. We show that BITC selectively induces apoptosis in senescent IPF fibroblasts by targeting AKT signal pathway. Intraperitoneal administration of BITC to an age-related lung fibrosis mouse model effectively depleted senescent lung fibroblasts and reversed persistent pulmonary fibrosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Our study reveals that BITC may be a promising therapeutic option for IPF and other age-related disease that progress with the accumulation of senescent fibroblasts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2025.1506518","type":"journal-article","created":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T07:42:21Z","timestamp":1746171741000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Benzyl isothiocyanate provokes senolysis by targeting AKT in senescent IPF fibroblasts and reverses persistent pulmonary fibrosis in aged mice"],"prefix":"10.3389","volume":"16","author":[{"given":"Rui","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiting","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinhui","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenshun","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"L1164","DOI":"10.1152\/ajplung.00220.2017","article-title":"IPF lung fibroblasts have a senescent phenotype","volume":"313","author":"\u00c1lvarez","year":"2017","journal-title":"Am. 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