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Their accumulation increases during aging and is accelerated by hyperglycemia, oxidative stress, inflammation, exogenous exposure, and impaired renal clearance. Although AGE biology has often been framed around the AGE\u2013RAGE\u2013oxidative stress axis, current evidence supports a broader systems\u2010level model in which AGE burden reflects the balance among formation, detoxification, tissue retention, and clearance. This review summarizes AGE chemistry, endogenous and exogenous sources, detoxification pathways, receptor systems, and mechanisms of AGE\u2010mediated tissue injury. We distinguish two complementary pathogenic routes: receptor\u2010independent structural damage, including protein dysfunction, proteostatic stress, extracellular matrix crosslinking, and altered tissue mechanics; and receptor\u2010dependent signaling, mainly through RAGE\u2010mediated redox\u2010inflammatory amplification. We then examine the clinical relevance of AGEs in diabetes, cardiovascular disease, chronic kidney disease, neurovascular and retinal dysfunction, fibrosis, and aging\u2010related tissue decline. Particular attention is given to compartment\u2010specific biomarker interpretation, because circulating free adducts, protein\u2010bound AGEs, tissue autofluorescence, dietary AGE estimates, and dicarbonyl stress markers are not interchangeable. Finally, we evaluate therapeutic strategies and propose a framework that matches each intervention to the relevant mechanism and can be tested clinically. In doing so, the review clarifies major conceptual and methodological uncertainties in AGE research and provides a foundation for more rigorous biomarker interpretation, study design, and clinical translation.<\/jats:p>","DOI":"10.1002\/mco2.71073","type":"journal-article","created":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:48:12Z","timestamp":1791899292000},"source":"Crossref","is-referenced-by-count":0,"title":["Advanced Glycation End Products: From Pathogenesis to Treatment"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5519-3418","authenticated-orcid":false,"given":"Tak\u2010Ho","family":"Lo","sequence":"first","affiliation":[{"name":"School of Life Sciences Guangzhou University  Guangdong China"},{"name":"Department of Health Technology and Informatics The Hong Kong Polytechnic University  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junying","family":"Zou","sequence":"additional","affiliation":[{"name":"School of Life Sciences Guangzhou University  Guangdong China"},{"name":"College of Biology Hunan University  Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyi","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Life Sciences Guangzhou University  Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaijun","family":"Lin","sequence":"additional","affiliation":[{"name":"School of Life Sciences Guangzhou University  Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minhui","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Life Sciences Guangzhou University  Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangqi","family":"Lu","sequence":"additional","affiliation":[{"name":"School of Life Sciences Guangzhou University  Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Life Sciences Guangzhou University  Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyao","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Health Technology and Informatics The Hong Kong Polytechnic University  Hong Kong China"},{"name":"School of Chemistry and Chemical Engineering Guangzhou University  Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,13]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/jf60015a004"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201308808"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10719-016-9709-8"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/414813a"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2018.08.014"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2022.11.004"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8070749"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00001.2019"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrestox.2c00160"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.2337\/db23-0277"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu11020215"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2023.101734"},{"key":"e_1_2_13_14_1","first-page":"1025","article-title":"Advanced Glycation Endproducts and Cigarette Smoking","volume":"44","author":"Nicholl I. 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