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On a molecular level, it significantly impacts the regulation of protein modifications, leading to the accumulation of degenerative protein modifications (DPMs) such as aberrant serine phosphorylation (p\u2010Ser) and trioxidized cysteine (t\u2010Cys) within the proteome. The altered p\u2010Ser is linked to abnormal cell signaling, while the accumulation of t\u2010Cys is associated with chronic diseases induced by oxidative stress. Despite this, the potential cross\u2010effects and functional interplay between these two critical molecular factors of aging remain undisclosed. This study analyzes the aging proteome of wild\u2010type C57BL\/6NTac mice over 2\u2009years using advanced proteomics and bioinformatics. Our objective is to provide a comprehensive analysis of how t\u2010Cys affects cell signaling and protein structure in the aging process. The results obtained indicate that t\u2010Cys residues accumulate in the aging proteome, interact with p\u2010Ser interacting enzymes, as validated in\u00a0vitro, and alter their structures similarly to p\u2010Ser. These findings have significant implications for understanding the interplay of oxidative stress and phosphorylation in the aging process. Additionally, they open new venues for further research on the role(s) of these protein modifications in various human chronic diseases and aging, wherein exacerbated oxidation and aberrant phosphorylation are implicated.<\/jats:p>","DOI":"10.1111\/acel.14062","type":"journal-article","created":{"date-parts":[[2023,12,19]],"date-time":"2023-12-19T10:14:57Z","timestamp":1702980897000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Trioxidized cysteine in the aging proteome mimics the structural dynamics and interactome of phosphorylated serine"],"prefix":"10.1111","volume":"23","author":[{"given":"Jose Antonio","family":"S\u00e1nchez\u00a0Mil\u00e1n","sequence":"first","affiliation":[{"name":"Biomedical Research Institute of Lleida (IRBLLEIDA) \u2010 +Pec Proteomics Research Group (+PPRG) \u2010 Neuroscience Area University Hospital Arnau de Vilanova (HUAV)  Lleida Spain"},{"name":"Department of Basic Medical 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