{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:43:09Z","timestamp":1785436989103,"version":"3.56.0"},"reference-count":35,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"JSPS","doi-asserted-by":"publisher","award":["17H06398"],"award-info":[{"award-number":["17H06398"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"award":["17H06398"],"award-info":[{"award-number":["17H06398"]}],"id":[{"id":"https:\/\/ror.org\/00hhkn466","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The senescence-associated secretory phenotype (SASP) contributes to various age-related pathologies. Methyl caffeate exhibits strong SASP-inhibitory activity; however, its molecular targets and the precise mechanisms underlying its effects remain unclear. Therefore, in this study, we performed affinity chromatography using methyl caffeate-immobilized beads to identify its intracellular binding proteins. The functional roles of the identified target were validated via knockdown experiments, assessment of SASP factor (interleukin [IL]-6 and IL-8) expression at the mRNA and secretion levels, and analysis of nuclear factor-\u03baB and p38 mitogen-activated protein kinase signaling pathways. IQ motif-containing GTPase-activating protein 1 (IQGAP1) was identified as a methyl caffeate-binding partner. IQGAP1 knockdown significantly reduced IL-6 and IL-8 expression levels, mimicking the effects of methyl caffeate treatment. Furthermore, IQGAP1 depletion suppressed nuclear factor-\u03baB activation and p38 phosphorylation. Overall, this study identified IQGAP1 as a critical scaffold protein essential for SASP induction and a target of methyl caffeate. Our findings provide key insights into SASP regulation, facilitating the development of SASP-modulating therapeutics targeting specific IQGAP1 domains.<\/jats:p>","DOI":"10.3390\/ijms27125199","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T09:46:54Z","timestamp":1780998414000},"page":"5199","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Methyl Caffeate Binds to IQGAP1 and Inhibits the Senescence-Associated Secretory Phenotype in Senescent Cells"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-5978-3199","authenticated-orcid":false,"given":"Shusuke","family":"Yasuda","sequence":"first","affiliation":[{"name":"Department of Drug Discovery Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosuke","family":"Iizumi","sequence":"additional","affiliation":[{"name":"Division of Immunology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Fukumuro, Miyagino-ku, Sendai 983-8536, Japan"},{"name":"Department of Molecular-Targeting Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mamiko","family":"Sukeno","sequence":"additional","affiliation":[{"name":"Department of Drug Discovery Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiyuki","family":"Sakai","sequence":"additional","affiliation":[{"name":"Department of Drug Discovery Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8168-1802","authenticated-orcid":false,"given":"Mano","family":"Horinaka","sequence":"additional","affiliation":[{"name":"Department of Drug Discovery Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1146\/annurev-physiol-030212-183653","article-title":"Aging, cellular senescence, and cancer","volume":"75","author":"Campisi","year":"2013","journal-title":"Annu. 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