{"doi":"10.18632/aging.206335","title":"Methylglyoxal-induced glycation stress promotes aortic stiffening: putative mechanistic roles of oxidative stress and cellular senescence","abstract":"BACKGROUND: Here, we assessed the role of the advanced glycation end-product (AGE) precursor methylglyoxal (MGO) and its non-crosslinking AGE MGO-derived hydroimidazolone (MGH)-1 in aortic stiffening and explored the potential of a glycation stress-lowering compound (Gly-Low) to mitigate these effects. METHODS: through elastic modulus. Putative mechanisms underlying MGO- and MGH-1-induced aortic stiffening were explored using complementary experimental approaches in aortic tissue and cultured human aortic endothelial cells (HAECs). Moreover, aortic stiffness was assessed in old C57BL/6J (24 month) mice after consumption of Gly-Low-enriched chow. RESULTS: MGO-induced glycation stress increased PWV in young mice by 21% (P<0.05 vs. control), which was prevented with Gly-Low (P=0.93 vs. control). Ex vivo, MGO increased aortic elastic modulus ~100% (P<0.05), superoxide production by ~40% (P<0.05), and MGH-1 expression by 50% (P<0.05), which were all mitigated by Gly-Low. Chronic MGO exposure elevated biomarkers of cellular senescence in HAECs, comparable to a known senescence inducer Doxorubicin, an effect partially blocked by Gly-Low. Moreover, elevated aortic elastic modulus induced by Doxorubicin (P<0.05 vs. control) was prevented with Gly-Low (P=0.71 vs. control). Aortic RNA sequencing implicated preservation of endogenous cellular detoxification pathways with Gly-Low following exposure to MGH-1. Old mice supplemented with Gly-Low had lower PWV (P<0.05) relative to old control mice. CONCLUSIONS: MGO-induced glycation stress contributes to aortic stiffening and glycation stress lowering compounds hold promise for mitigating these effects.","journal":"Aging","year":2025,"id":548528,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9685,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":970568,"name":"Ravinandan Venkatasubramanian","orcid":null,"position":1,"is_corresponding":false},{"id":753449,"name":"Sophia Mahoney","orcid":"0000-0002-0013-4514","position":2,"is_corresponding":false},{"id":1022016,"name":"Mary A. Darrah","orcid":null,"position":3,"is_corresponding":false},{"id":514532,"name":"Katelyn R. Ludwig","orcid":"0009-0005-0592-2711","position":4,"is_corresponding":false},{"id":1369588,"name":"Alice Zhang","orcid":"0000-0001-5094-6898","position":5,"is_corresponding":false},{"id":377100,"name":"Kiyomi R. Kaneshiro","orcid":"0000-0003-0636-7455","position":6,"is_corresponding":false},{"id":1442234,"name":"Lizbeth Enriquez Najera","orcid":null,"position":7,"is_corresponding":false},{"id":1441725,"name":"Lauren Wimer","orcid":"0009-0009-2104-9501","position":8,"is_corresponding":false},{"id":997007,"name":"Muniesh Muthaiyan Shanmugam","orcid":"0000-0001-8018-2032","position":9,"is_corresponding":false},{"id":1442235,"name":"Edgard Morazan","orcid":null,"position":10,"is_corresponding":false},{"id":427807,"name":"James J. Galligan","orcid":"0000-0001-7882-5596","position":11,"is_corresponding":false},{"id":1442236,"name":"Marrisa N. Trujillo","orcid":null,"position":12,"is_corresponding":false},{"id":308347,"name":"Richmond Sarpong","orcid":"0000-0002-0028-6323","position":13,"is_corresponding":false},{"id":307108,"name":"Douglas R. Seals","orcid":"0000-0002-2391-9824","position":14,"is_corresponding":false},{"id":110393,"name":"Pankaj Kapahi","orcid":"0000-0002-5629-4947","position":15,"is_corresponding":false},{"id":307104,"name":"Zachary S. Clayton","orcid":"0000-0003-3878-3533","position":16,"is_corresponding":false},{"id":551620,"name":"Parminder Singh","orcid":"0000-0002-2851-6805","position":0,"is_corresponding":true}],"reference_count":39,"raw_metadata":null,"created_at":"2026-07-19T02:53:58.530220Z","pmid":"41247756","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}