{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:15:22Z","timestamp":1782087322135,"version":"3.54.5"},"reference-count":12,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP16H02667"],"award-info":[{"award-number":["JP16H02667"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp;amp; Perspec"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Environmental stressors, such as ionizing radiation, accelerate aging by causing DNA damage and triggering pathways that lead to cell cycle arrest, apoptosis, and subsequent inflammation. The thrombopoietin receptor agonist romiplostim (RP), which is used as a clinical treatment for chronic idiopathic thrombocytopenic purpura and aplastic anemia, is known to be promising in reducing radiation\u2010induced tissue damage. In this study, we established a mouse model of radiation\u2010induced premature aging to evaluate the potential of RP in ameliorating this process. Female C57BL\/6JJcl mice were subjected to total body irradiation with various irradiation schedules. Mice irradiated with 5\u2009Gy every 4\u2009weeks (total dose of 10\u2009Gy over 2\u2009months) showed a significant aging phenotype, including graying hair and elevated serum aging markers (CDKN2A\/p16\n                    <jats:sup>INK4a<\/jats:sup>\n                    , tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1), and C\u2010reactive protein), compared with sham\u2010irradiated controls. RP was intraperitoneally administered to the mouse model (10\u2009\u03bcg\/kg weekly or 50\u2009\u03bcg\/kg every 4\u2009weeks). Treatment significantly reduced TNF\u2010\u03b1 levels by 15% and the area of graying body hair by 70%. Although bone marrow cell recovery was incomplete, spleen cell counts were significantly restored (2\u2010fold) by 50\u2009\u03bcg\/kg RP, and SA\u2010\u03b2\u2010gal activity, a marker of cellular senescence, was also significantly suppressed by approximately 15%. These findings suggest that RP may partially ameliorate radiation\u2010induced premature aging, providing a basis for future research addressing health issues associated with aging and radiation exposure.\n                  <\/jats:p>","DOI":"10.1002\/prp2.70203","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T09:52:43Z","timestamp":1764582763000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Effect of Thrombopoietin Receptor Agonist Romiplostim on the Ionizing Radiation\u2010Induced Premature Aging"],"prefix":"10.1002","volume":"13","author":[{"given":"Masaru","family":"Yamaguchi","sequence":"first","affiliation":[{"name":"Department of Radiation Science Hirosaki University Graduate School of Health Sciences  Hirosaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tokuhisa","family":"Hirouchi","sequence":"additional","affiliation":[{"name":"Department of Radiobiology Institute for Environmental Sciences  Rokkasho Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3375-5189","authenticated-orcid":false,"given":"Yoshiaki","family":"Sato","sequence":"additional","affiliation":[{"name":"Norris Comprehensive Cancer Center University of Southern California  California Los Angeles USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikuo","family":"Kashiwakura","sequence":"additional","affiliation":[{"name":"Department of Radiation Science Hirosaki University Graduate School of Health Sciences  Hirosaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010022\u201001251\u20100"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2018.00522"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12030651"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semradonc.2021.11.011"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2019.03.023"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010018\u201029013\u20105"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287\u2010020\u201001861\u2010x"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423\u2010023\u201001072\u20103"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2013.155"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/adbi.202400079"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2022.111706"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.7754\/Clin.Lab.2021.210731"}],"container-title":["Pharmacology Research &amp; Perspectives"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/prp2.70203","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T16:56:34Z","timestamp":1765817794000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1002\/prp2.70203"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":12,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1002\/prp2.70203"],"URL":"https:\/\/doi.org\/10.1002\/prp2.70203","archive":["Portico"],"relation":{},"ISSN":["2052-1707","2052-1707"],"issn-type":[{"value":"2052-1707","type":"print"},{"value":"2052-1707","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"2025-08-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70203"}}