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In this study, we investigated the anti-aging mechanism of Camellia japonica flower (CJF) extract and its active ingredient hyperoside based on a doxorubicin (DOX)-induced endogenous senescence model in human skin fibroblasts (HSFs). LC-MS proteomics analysis revealed that CJF extract and hyperoside specifically activated the FUNDC1-mediated mitochondrial autophagy pathway, significantly ameliorated the DOX-induced decrease in mitochondrial membrane potential and the accumulation of reactive oxygen species (ROS), and alleviated the cellular S-phase blockade and reversed the high expression of senescence-associated \u03b2-galactosidase (SA-\u03b2-gal). Further studies showed that the two cleared damaged mitochondria by enhancing mitochondrial autophagy and restoring cellular energy metabolism homeostasis while promoting type III collagen and elastin synthesis and repairing the expression of Claudin 1 related to skin barrier function. For the first time, the present study reveals the molecular mechanism of CJF extract in delaying skin aging by regulating the FUNDC1-dependent mitochondrial autophagy pathway, which provides a theoretical basis and a candidate strategy for developing novel anti-aging agents targeting mitochondrial quality control.<\/jats:p>","DOI":"10.3390\/antiox14080968","type":"journal-article","created":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T10:58:26Z","timestamp":1754564306000},"page":"968","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Camellia japonica Flower Extract and the Active Constituent Hyperoside Repair DNA Damage Through FUNDC1-Mediated Mitophagy Pathway for Skin Anti-Aging"],"prefix":"10.3390","volume":"14","author":[{"given":"Hongqi","family":"Gao","sequence":"first","affiliation":[{"name":"School of Pharmacy, Guangdong Engineering Technology Research Centre of Molecular Probe and Biomedicine Imaging, Guangdong Pharmaceutical University, Guangzhou 510006, China"},{"name":"Shanghai Forest Cabin Biological-Tech Co., Ltd., Shanghai 201600, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahui","family":"Shi","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Guangdong Engineering Technology Research Centre of Molecular Probe and Biomedicine Imaging, Guangdong Pharmaceutical University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangtao","family":"Li","sequence":"additional","affiliation":[{"name":"Shanghai Forest Cabin Biological-Tech Co., Ltd., Shanghai 201600, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhifang","family":"Lai","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Guangdong Engineering Technology Research Centre of Molecular Probe and Biomedicine Imaging, Guangdong Pharmaceutical University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Guangdong Engineering Technology Research Centre of Molecular Probe and Biomedicine Imaging, Guangdong Pharmaceutical University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chanling","family":"Yuan","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Guangdong Engineering Technology Research Centre of Molecular Probe and Biomedicine Imaging, Guangdong Pharmaceutical University, Guangzhou 510006, China"},{"name":"Guangzhou Ruby Biotechnology Co., Ltd., Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjie","family":"Mei","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Guangdong Engineering Technology Research Centre of Molecular Probe and Biomedicine Imaging, Guangdong Pharmaceutical University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.cytogfr.2024.07.009","article-title":"Uncovering key mechanisms and intervention therapies in aging skin","volume":"79","author":"Zhang","year":"2024","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1038\/s43587-021-00150-3","article-title":"Molecular Damage in Aging","volume":"1","author":"Gladyshev","year":"2021","journal-title":"Nat. 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