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Currently, from the perspective of regulating senescent cells, potent compounds or reliable protein targets that could effectively prevent skin photoaging have not yet been reported. Herein, we demonstrated that chlorogenic acid (CGA) significantly inhibited UVA\u2010induced senescence of human dermis skin fibroblasts (HDF) cells by screening the natural product library. The activity\u2010based protein profiling (ABPP) result revealed that Enolase 1 (ENO1) is one of the direct targets of CGA in HDF cells. Further mechanism research indicated that CGA covalently binds to ENO1, and prevented UVA\u2010induced cellular senescence by suppressing the activity of ENO1 protein to block the glycolytic pathway. Importantly, we found that CGA dose\u2010dependently reduced the skin wrinkle score, alleviated skin pathological features and inhibited senescent characteristics in a photoaging mouse model. The proteomic analysis revealed that CGA treatment effectively inhibited senescence\u2010associated secretory phenotype (SASP) secretion and glycolysis in skin samples of mice. Collectively, our study not only demonstrated that inhibiting cell senescence is an effective anti\u2010skin photoaging strategy, but also revealed that ENO1 is a promising protein target to prevent photoaging.<\/jats:p>","DOI":"10.1111\/acel.14433","type":"journal-article","created":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T05:40:21Z","timestamp":1735710021000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Identifying <scp>ENO1<\/scp> as a protein target of chlorogenic acid to inhibit cellular senescence and prevent skin photoaging in mice"],"prefix":"10.1111","volume":"24","author":[{"given":"Xueling","family":"He","sequence":"first","affiliation":[{"name":"State Key Laboratory for Quality Ensurance and Sustainable Use of Dao\u2010di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences  Beijing China"},{"name":"Department of Urology, The Second Clinical Medical College Jinan University (Shenzhen People's Hospital)  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Quality Ensurance and Sustainable Use of Dao\u2010di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Quality Ensurance and Sustainable Use of Dao\u2010di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Quality Ensurance and Sustainable Use of 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