Associations of proteomic age clocks with lifestyle risk factors, incident chronic diseases and mortality in two European cohorts
Assessment of biological aging using proteomic clocks may enhance risk prediction and elucidate the molecular links between aging and chronic diseases. Here, among 17,473 participants of the European Prospective Investigation into Cancer and Nutrition, we examined associations of plasma SomaScan-based proteomic clocks, including organ-specific clocks, with risk factors, 24 incident chronic diseases and all-cause mortality, over up to 28 years of follow-up. Replication was conducted in the Whitehall II study. We show that the global age gap, an age acceleration score combining proteomic clocks, was associated with smoking, alcohol consumption, physical inactivity and higher risk of mortality, cardiovascular diseases, dementia and cancers of the liver, upper aero-digestive tract, lung and kidney. Lung, kidney and stomach cancers were more strongly associated with related organ-specific age gaps. Predictive performance of proteomic clocks for mortality was comparable to that of classical lifestyle risk factors. In summary, proteomic clocks appear promising biomarkers of generalized age-related disease risk.
Authors
- Philipp Frank (ORCID: https://orcid.org/0000-0001-8824-8673)
- Christina M. Lill (ORCID: https://orcid.org/0000-0002-2805-1307)
- Chung‐Ho E. Lau (ORCID: https://orcid.org/0000-0002-3602-8326)
- Salvatore Panico (ORCID: https://orcid.org/0000-0002-5498-8312)
- Oliver Robinson (ORCID: https://orcid.org/0000-0002-4735-0468)
- Mika Kivimaki B (ORCID: https://orcid.org/0000-0002-4699-5627)
- Roel C.H. Vermeulen (ORCID: https://orcid.org/0000-0003-4082-8163)
- Rudolf Kaaks (ORCID: https://orcid.org/0000-0003-3751-3929)
- Han Xiao (ORCID: https://orcid.org/0000-0002-6108-2789)
- N. Charlotte Onland‐Moret (ORCID: https://orcid.org/0000-0002-2360-913X)
- Fulvio Ricceri (ORCID: https://orcid.org/0000-0001-8749-9737)
- Karl Smith-Byrne (ORCID: https://orcid.org/0000-0002-1932-7463)
- Claudia Langenberg (ORCID: https://orcid.org/0000-0002-5017-7344)
- Vivian Viallon (ORCID: https://orcid.org/0000-0002-9799-4421)
- Jan Homann (ORCID: https://orcid.org/0000-0003-2791-7065)
- Elio Ríboli (ORCID: https://orcid.org/0000-0001-6795-6080)
- Anna E. Prizment (ORCID: https://orcid.org/0000-0001-5924-6871)
- Paolo Vineis (ORCID: https://orcid.org/0000-0001-8935-4566)
- Nicholas J. Wareham (ORCID: https://orcid.org/0000-0003-1422-2993)
- Lefkos Middleton (ORCID: https://orcid.org/0000-0002-2176-403X)
- P.J. Medina Sánchez
- Verena A. Katzke
- W. M. Monique Verschuren
- Ana Jiménez Zabala
- Marc J. Gunter
- Pietro Ferrari
- José M. Huerta
- Shuo Wang
Institutions
- University of Minnesota (US)
- University of Helsinki (FI)
- Queen Mary University of London (GB)
- German Cancer Research Center (DE)
- Utrecht University (NL)
- Heidelberg University (DE)
- University of Münster (DE)
- University of Cambridge (GB)
- Basque Government (ES)
- University Medical Center Utrecht (NL)
- University of Oxford (GB)
- Ministry of Health (ES)
- National Institute for Public Health and the Environment (NL)
- Instituto de Investigación Biosanitaria de Granada (ES)
- Federico II University Hospital (IT)
- UK Dementia Research Institute (GB)
- Berlin Institute of Health at Charité - Universitätsmedizin Berlin (DE)
- MRC Unit for Lifelong Health and Ageing (GB)
- Onkologikoa (ES)
- Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (ES)
- MRC Epidemiology Unit (GB)
- Centre international de recherche sur le cancer (FR)
- University College London (GB)
- Imperial College London (GB)
- University of Turin (IT)
- Andalusian School of Public Health (ES)
Publication Details
- Journal
- Nature Aging
- Published
- 2026-06-29
- DOI
- https://doi.org/10.1038/s43587-026-01163-6
- Primary Topic
- Circadian rhythm and melatonin
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Compagnia di San Paolo
- Cure Alzheimer's Fund
- UK Research and Innovation
- Cancer Research UK
- National Institute for Health and Care Research
- Imperial College London
- European Commission
- Deutsche Forschungsgemeinschaft
- ZonMw
- Ministero della Salute
- Associazione Italiana per la Ricerca sul Cancro
- Medical Research Council
- World Cancer Research Fund
- Instituto de Salud Carlos III
- NIHR Imperial Biomedical Research Centre
- School of Public Health, Imperial College London
- National Cancer Institute
- National Center for Advancing Translational Sciences