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Here, we conducted a cross\u2010sectional observational study of coffee consumption and a 1\u2010month clinical trial in humans. We found that coffee consumption significantly reshaped the immune system and metabolism, including reduced levels of inflammatory factors and a reduced frequency of senescent T cells. The frequency of senescent T cells and the levels of the senescence\u2010associated secretory phenotype were lower in both long\u2010term coffee consumers and new coffee consumers than in coffee nondrinking subjects, suggesting that coffee has anti\u2010immunosenescence effects. Moreover, coffee consumption downregulated the activities of the The Janus kinase\/signal transduction and activator of transcription (JAK\/STAT) and mitogen\u2010activated protein kinases (MAPK) signaling pathways and reduced systemic proinflammatory cytokine levels. Mechanistically, coffee\u2010associated metabolites, such as 1\u2010methylxanthine, 3\u2010methylxanthine, paraxanthine, and ceramide, reduced the frequency of senescent CD4<jats:sup>+<\/jats:sup>CD57<jats:sup>+\u2005<\/jats:sup>T cells in vitro. Finally, in vivo, coffee intake alleviated inflammation and immunosenescence in imiquimod\u2010induced psoriasis\u2010like mice. Our results provide novel evidence of the anti\u2010inflammatory and anti\u2010immunosenescence effects of coffee, suggesting that coffee consumption could be considered a healthy habit.<\/jats:p>","DOI":"10.1002\/mco2.617","type":"journal-article","created":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T15:14:11Z","timestamp":1718637251000},"source":"Crossref","is-referenced-by-count":10,"title":["Metabolic shifts during coffee consumption refresh the immune response: insight from comprehensive multiomics analysis"],"prefix":"10.1002","volume":"5","author":[{"given":"Pinglang","family":"Ruan","sequence":"first","affiliation":[{"name":"Department of Dermatology The Second Xiangya Hospital, Central South University Hunan Key Laboratory of Medical Epigenomics  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Dermatology The Second Xiangya Hospital, Central South 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