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BackgroundEpigenetic age acceleration (an older methylation age compared to chronological age) correlates strongly with various age-related morbidities and mortality. Chronic systemic inflammation is thought to be a hallmark of ageing, but the relationship between an increased epigenetic age and this likely key phenotype of ageing has not yet been extensively investigated.MethodsWe modelled the trajectories of the inflammatory biomarkers C-reactive protein (CRP; measured using both a high- and low-sensitivity assay) and interleukin-6 (IL-6) over the eighth decade in the Lothian Birth Cohort 1936. Using linear mixed models, we investigated the association between CRP and immune cell profiles imputed from the methylation data and examined the cross-sectional and longitudinal association between the inflammatory biomarkers and two measures of epigenetic age acceleration, derived from the Horvath and Hannum epigenetic clocks.ResultsWe found that low-sensitivity CRP declined, high-sensitivity CRP did not change, and IL-6 increased over time within the cohort. CRP levels inversely associated with CD8+T cells and CD4+T cells and positively associated with senescent CD8+T cells, plasmablasts and granulocytes. Cross-sectionally, the Hannum, but not the Horvath, measure of age acceleration was positively associated with each of the inflammatory biomarkers, including a restricted measure of CRP (≤ 10 mg/L) likely reflecting levels relevant to chronic inflammation.ConclusionsWe found a divergent relationship between inflammation and immune system parameters in older age. We additionally report the Hannum measure of epigenetic age acceleration associated with an elevated inflammatory profile cross-sectionally, but not longitudinally.

Original publication




Journal article


Clinical epigenetics

Publication Date





Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.


Plasma Cells, Granulocytes, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Humans, Inflammation, C-Reactive Protein, Genetic Markers, Interleukin-6, Lymphocyte Count, Linear Models, Longitudinal Studies, Cross-Sectional Studies, DNA Methylation, Epigenesis, Genetic, Aging, Aged, Aged, 80 and over, Female, Male