Associations of proteomic age with mortality and incident chronic diseases in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Associations of proteomic age with mortality and incident chronic diseases in the European Prospective Investigation into Cancer and Nutrition (EPIC) | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Associations of proteomic age with mortality and incident chronic diseases in the European Prospective Investigation into Cancer and Nutrition (EPIC) Oliver Robinson, Han Xiao, Jan Homann, Vivian Viallon, Pietro Ferrari, and 21 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7087230/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Assessment of biological ageing using proteomic clocks may enhance risk prediction and elucidate the molecular links between ageing and chronic diseases. Within a pre-diagnostic cohort of 17,473 Europeans with up to 28 years of follow-up, we examined associations of plasma SomaScan-based proteomic clocks, including organ-specific clocks, with 24 incident chronic diseases, all-cause mortality, and lifestyle risk factors. Global proteomic age gap (a composite biological age acceleration score combining previously published clocks) showed the strongest positive association of all tested clocks with all-cause mortality. Accelerated proteomic ageing was significantly associated with smoking, alcohol consumption, physical inactivity, and higher risk of cardiovascular diseases, dementia, and liver, upper aero-digestive tract, lung, and kidney cancers. Some organ-specific cancers were more strongly associated with their respective organ-specific age gaps. Mortality prediction by proteomic clocks was comparable in performance to classical lifestyle risk factors. In summary, proteomic clocks appear promising biomarkers of generalized age-related disease risk. Health sciences/Biomarkers/Predictive markers Biological sciences/Computational biology and bioinformatics/Machine learning Aging biological age biological clocks neurodegeneration cancer cardiovascular disease diabetes risk factors risk prediction proteomics SomaLogic aptamers Full Text Additional Declarations There is NO Competing Interest. Supplementary Files EpicProteomicsbiomarkersofageingsupplementarytables.docx Supplementary tables EpicProteomicsbiomarkersofageingsupplementaryfigures.docx Supplementary Figures Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7087230","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":485103100,"identity":"76a5679e-4599-477d-bb45-9dd3b2c699ce","order_by":0,"name":"Oliver Robinson","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABBUlEQVRIiWNgGAWjYJACZgYDMHXgAIhiY2BuAAtLENbClgDVwkiMFjDgMYDyCWjhZ+B9+Lig4I49v3TPx0M3d9jk87EfbGD4UcOQOLMBuxbJBnZj4xkGzxJnzjm74XDumTTLNp7EBsaeYwyJs3HYYnCAjU2ax+BwgsGNXKCWtsMGbAyJDQy8DQyJ8whosTe4kfMAqOW/ARv/wwbGv0RoYdxwI4cBqOWAAZtEYgMzyBZcDpNsZmMG+uVw4swZaQZAvyQDtTxsOCxzTMIYl/f52dsYHxf8OWzPL5H8+HPuDjsD+f7kgw/f1NjIzjiAwxpmZA40RhgO4I9IbFpGwSgYBaNgFCADAKAsV7Ca5irDAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0002-4735-0468","institution":"Imperial College London","correspondingAuthor":true,"prefix":"","firstName":"Oliver","middleName":"","lastName":"Robinson","suffix":""},{"id":485103101,"identity":"301e406d-0501-4c8d-84ba-509ae5944f8b","order_by":1,"name":"Han Xiao","email":"","orcid":"","institution":"Imperial College London","correspondingAuthor":false,"prefix":"","firstName":"Han","middleName":"","lastName":"Xiao","suffix":""},{"id":485103102,"identity":"d59c1a8e-b082-42a1-8907-c62f2f3ed10e","order_by":2,"name":"Jan Homann","email":"","orcid":"https://orcid.org/0000-0003-2791-7065","institution":"University of Münster","correspondingAuthor":false,"prefix":"","firstName":"Jan","middleName":"","lastName":"Homann","suffix":""},{"id":485103103,"identity":"ddb9a548-842f-4ce7-92a4-9abeb84da0cc","order_by":3,"name":"Vivian Viallon","email":"","orcid":"","institution":"International Agency for Research on Cancer (IARC-WHO), Lyon, France","correspondingAuthor":false,"prefix":"","firstName":"Vivian","middleName":"","lastName":"Viallon","suffix":""},{"id":485103104,"identity":"ba695766-ef7c-4f60-8953-2404076b7fb4","order_by":4,"name":"Pietro Ferrari","email":"","orcid":"","institution":"International Agency for Research on Cancer (IARC-WHO)","correspondingAuthor":false,"prefix":"","firstName":"Pietro","middleName":"","lastName":"Ferrari","suffix":""},{"id":485103105,"identity":"b9ebb2f2-be69-40b0-b11d-fdff2e5ea944","order_by":5,"name":"José Huerta","email":"","orcid":"","institution":"Department of Epidemiology, Murcia Regional Health Council, Biomedical Research Institute of Murcia-IMIB, 30007 Murcia, Spain","correspondingAuthor":false,"prefix":"","firstName":"José","middleName":"","lastName":"Huerta","suffix":""},{"id":485103106,"identity":"a85bec19-630e-46f0-a292-9827aa3380a3","order_by":6,"name":"Ana Jiménez-Zabala","email":"","orcid":"","institution":"Biogipuzkoa Health Research Institute, San Sebastian, Gipuzkoa, Spain","correspondingAuthor":false,"prefix":"","firstName":"Ana","middleName":"","lastName":"Jiménez-Zabala","suffix":""},{"id":485103107,"identity":"d0092724-9b06-44f5-b108-0ef8740e9d8a","order_by":7,"name":"Rudolf Kaaks","email":"","orcid":"https://orcid.org/0000-0003-3751-3929","institution":"German Cancer Research Center (DKFZ); Translational Lung Research Center (TLRC) Heidelberg","correspondingAuthor":false,"prefix":"","firstName":"Rudolf","middleName":"","lastName":"Kaaks","suffix":""},{"id":485103108,"identity":"1969c881-fcc4-4c78-95cd-2d608cce5680","order_by":8,"name":"Verena Katzke","email":"","orcid":"","institution":"German Cancer Research Center (DKFZ)","correspondingAuthor":false,"prefix":"","firstName":"Verena","middleName":"","lastName":"Katzke","suffix":""},{"id":485103109,"identity":"267efcf2-8d56-41c9-a7cf-c7a21f2ad81f","order_by":9,"name":"Claudia Langenberg","email":"","orcid":"https://orcid.org/0000-0002-5017-7344","institution":"Queen Mary University of London","correspondingAuthor":false,"prefix":"","firstName":"Claudia","middleName":"","lastName":"Langenberg","suffix":""},{"id":485103110,"identity":"65863680-6c1f-4bbc-a388-fb94112e9a74","order_by":10,"name":"Chung-Ho Lau","email":"","orcid":"https://orcid.org/0000-0002-3602-8326","institution":"Imperial College London","correspondingAuthor":false,"prefix":"","firstName":"Chung-Ho","middleName":"","lastName":"Lau","suffix":""},{"id":485103111,"identity":"9cd2bca9-e1bd-4f33-9290-f6dd068a3cd4","order_by":11,"name":"Lefkos Middleton","email":"","orcid":"https://orcid.org/0000-0002-2176-403X","institution":"Imperial College London","correspondingAuthor":false,"prefix":"","firstName":"Lefkos","middleName":"","lastName":"Middleton","suffix":""},{"id":485103112,"identity":"f3996de9-0816-45ae-969c-f70896a6ef58","order_by":12,"name":"N. 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