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Folic acid (FA), a water\u2010soluble vitamin, plays critical roles in DNA synthesis\/repair, cell cycle regulation, epigenetic regulation via methylation, oxidative stress response, and embryonic development. However, its radioprotective role has not been systematically elucidated. This study aimed to investigate its effects and molecular mechanisms during RILI. The RILI murine model showed that folic acid supplementation significantly alleviated radiation\u2010induced lung tissue damage, body weight loss, and inflammatory cell infiltration. Meanwhile, folic acid mitigated radiation\u2010induced DNA damage and cellular senescence in lung tissues and lung epithelial cell lines. RNA sequencing identified a 29\u2010gene SASP signature (including CCL5, CXCL2, CXCL10), which was significantly suppressed by folic acid in irradiated lungs. Moreover, folic acid inhibited SASP production by suppressing the phosphorylation of P38 MAPK\/NF\u2010\u03baB signaling pathway. By integrating in vivo and in vitro models, we revealed that folic acid exerts its radioprotective effects by reducing cellular senescence and the production of SASP. Taken together, these findings indicated that folic acid is potentially a novel therapeutic strategy for RILI.<\/jats:p>","DOI":"10.1002\/mc.70027","type":"journal-article","created":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T12:08:07Z","timestamp":1756123687000},"page":"1913-1925","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Folic Acid Protects Against Radiation\u2010Induced Lung Injury by Suppressing Senescence of Lung Epithelial Cells"],"prefix":"10.1002","volume":"64","author":[{"given":"Li","family":"Zhong","sequence":"first","affiliation":[{"name":"Department of Cancer Center Army Medical Center of PLA Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Cancer Center Army Medical Center of PLA Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuxin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Cancer Center Army Medical Center of PLA Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Jian","sequence":"additional","affiliation":[{"name":"Department of Cancer Center Army Medical Center of PLA Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Cancer Center Army Medical Center of PLA Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xianfeng","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Cancer Center Army Medical Center of PLA Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,8,25]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semradonc.2020.11.006"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2009.06.091"},{"issue":"1","key":"e_1_2_11_4_1","first-page":"37","article-title":"Radiation\u2010Induced Lung Injury. 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