{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T10:10:50Z","timestamp":1790071850838,"version":"4.0.1"},"reference-count":83,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>Platelet-derived growth factor-BB (PDGF-BB), a core functional isoform of the PDGF family, serves as a central regulator of cell proliferation, migration, differentiation, and tissue remodeling. Extensive preclinical and clinical evidence indicates that PDGF-BB expression exhibits profound spatiotemporal heterogeneity during natural aging and across various pathological conditions, including cardiovascular, neurodegenerative, and musculoskeletal diseases, as well as malignancies. Importantly, these dynamic expression patterns are intrinsically linked to disease progression and distinct aging phenotypes. Mechanistically, PDGF-BB initiates complex intracellular signaling cascades\u2014such as the ERK, JNK, PI3K-AKT, and mTOR pathways\u2014via specific engagement with PDGFR\u03b1\/\u03b2 dimers. Through these networks, PDGF-BB orchestrates intercellular communication and maintains microenvironmental homeostasis in a highly dose-dependent and cell-type-specific manner. Consequently, pharmacological interventions using small molecules, natural products, and biological agents have demonstrated efficacy in modulating PDGF-BB expression and its downstream signaling, presenting promising therapeutic targets for aging-related disorders and associated tissue damage. This review systematically synthesizes the heterogeneous expression profiles of PDGF-BB across natural aging and diverse disease contexts. We delineate the molecular mechanisms underlying its role in driving senescence and pathological progression, and critically evaluate the translational potential and current limitations of PDGF-BB-targeted therapies. By comprehensively mapping the biological network of PDGF-BB, this review aims to provide a conceptual framework for future basic research and clinical translation.<\/jats:p>","DOI":"10.3389\/fcell.2026.1926050","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T09:41:55Z","timestamp":1790070115000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Platelet-derived growth factor-BB (PDGF-BB): pathophysiological roles and therapeutic implications in aging-related diseases"],"prefix":"10.3389","volume":"14","author":[{"given":"Miao","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Orthopaedics, The Second Affiliated Hospital of Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Huang","sequence":"additional","affiliation":[{"name":"Orthopaedic Institute, Wuxi Ninth People\u2019s Hospital Affiliated to Soochow University","place":["Wuxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanshi","family":"She","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Qian","sequence":"additional","affiliation":[{"name":"Division of Orthopaedics, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People\u2019s Hospital","place":["Quzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Quzhou Key Laboratory of Aging Biology and Longevity Medicine, Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People\u2019s Hospital","place":["Quzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaocheng","family":"Zhai","sequence":"additional","affiliation":[{"name":"Division of Orthopaedics, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People\u2019s Hospital","place":["Quzhou, China"]},{"name":"Quzhou Key Laboratory of Aging Biology and Longevity Medicine, Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People\u2019s Hospital","place":["Quzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1382","DOI":"10.4254\/wjh.v14.i7.1382","article-title":"Transcriptome changes in stages of non-alcoholic fatty liver disease","volume":"14","author":"Aljabban","year":"2022","journal-title":"World J. 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