Abstract
DNA methylation-based epigenetic clocks are reliable measures of biological age and aging rate. Chronic inflammation may contribute to aging and various diseases, but population-based studies on specific inflammatory biomarkers’ impact on epigenetic clocks are limited. The aim of this study was to investigate the associations between 38 circulating inflammatory biomarkers, as well as a combined systemic inflammation variable, and epigenetic clocks in a middle-aged population. The cohort included 1,327 Finnish participants (aged 30–45 years, 50–55% female) from the Young Finns Study. Biomarkers were measured in 2007, and epigenetic clocks were assessed in 2011 and 2018. DunedinPACE and PCGrimAgeDev clocks were calculated using blood methylation data. Multiple linear regression models adjusted for age, sex, BMI, smoking, socioeconomic status, alcohol consumption, and physical activity were used. Results showed 11 biomarkers positively associated with DunedinPACE across both follow-ups. Seven biomarkers were positively associated with PCGrimAgeDev in the 4-year follow-up, but not in the 11-year follow-up. The combined systemic inflammation marker was positively associated with both clocks in both follow-ups. Although previous cross-sectional studies have reported associations between pro-inflammatory cytokines and epigenetic ageing, longitudinal findings remain sparse. Our results extend this literature by showing that several cytokines predict accelerated epigenetic ageing across an 11-year follow-up.
Data availability
The dataset supporting the conclusions of this article were obtained from the Cardiovascular Risk in Young Finns study which comprises health related participant data. The use of data is restricted under the regulations on professional secrecy (Act on the Openness of Government Activities, 612/1999) and on sensitive personal data (Personal Data Act, 523/1999, implementing the EU data protection directive 95/46/EC). Due to these restrictions, the data cannot be stored in public repositories or otherwise made publicly available. Data access may be permitted on a case-by-case basis upon request only. Data sharing outside the group is done in collaboration with YFS group and requires a data-sharing agreement. Investigators can submit an expression of interest to the chairman of the publication committee, Prof Olli Raitakari (University of Turku, Finland), Prof Mika Kähönen (Tampere University, Finland) and Prof Terho Lehtimäki (Tampere University, Finland). Requests to access these datasets should be directed to OR, olli.raitakari@utu.fi; TL, terho.lehtimaki@tuni.fi; MK, mika.kahonen@tuni.fi.
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Funding
The Young Finns Study has been financially supported by the Academy of Finland: grants 356405, 322098, 286284, 134309 (Eye), 126925, 121584, 124282, 349708, 330809, 338395, 129378 (Salve), 117797 (Gendi), and 141071 (Skidi); the Social Insurance Institution of Finland; Competitive State Research Financing of the Expert Responsibility area of Kuopio, Tampere and Turku University Hospitals (grant X51001); Juho Vainio Foundation; Paavo Nurmi Foundation; Finnish Foundation for Cardiovascular Research; Finnish Cultural Foundation; The Sigrid Juselius Foundation; Tampere Tuberculosis Foundation; Emil Aaltonen Foundation; Yrjö Jahnsson Foundation; Signe and Ane Gyllenberg Foundation; Diabetes Research Foundation of Finnish Diabetes Association; EU Horizon 2020 (grant 755320 for TAXINOMISIS and grant 848146 for To Aition); European Research Council (grant 742927 for MULTIEPIGEN project); Tampere University Hospital Supporting Foundation; Finnish Society of Clinical Chemistry; the Cancer Foundation Finland; pBETTER4U_EU (Preventing obesity through Biologically and bEhaviorally Tailored inTERventions for you; project number: 101080117); CVDLink (EU grant nro. 101137278) and the Jane and Aatos Erkko Foundation. Pashupati P. Mishra was supported by the Academy of Finland (Grant number: 349708) and Emma Raitoharju (grants: 330809, 338395) and the Jane and Aatos Erkko Foundation.
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LH: conducted the statistical analyses and wrote the initial draft. T.L., M.K., and O.R. contributed to data collection. MS. And SJ. were responsible for cytokine measurements. P.P.M contributed to data preprocessing and supervised the data analysis. All authors contributed to commenting and writing of the manuscript.
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Artificial intelligence was used to assist with language editing during manuscript preparation. Specifically, generative artificial intelligence tools were employed for grammar correction, clarity improvements, and stylistic consistency. All content was reviewed and approved by the authors.
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Humaloja, L., Marttila, S., Raitoharju, E. et al. Longitudinal association of circulating inflammatory biomarkers with epigenetic ageing in the Young Finns Study. Sci Rep (2026). https://doi.org/10.1038/s41598-026-46275-6
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DOI: https://doi.org/10.1038/s41598-026-46275-6
