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Trajectories of inflammatory biomarkers over the eighth decade and their associations with immune cell counts and epigenetic ageing

By Anna J Stevenson, Daniel L. McCartney, Sarah E Harris, Adele M. Taylor, Paul Redmond, John M. Starr, Qian Zhang, Allan F McRae, Naomi R. Wray, Tara L Spires-Jones, Barry W McColl, Andrew M. McIntosh, Ian J Deary, Riccardo E. Marioni

Posted 24 Aug 2018
bioRxiv DOI: 10.1101/397877

BACKGROUND: Epigenetic 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. METHODS: We 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 8th decade in the Lothian Birth Cohort 1936. We additionally investigated the association between CRP and imputed leukocyte counts. Using linear mixed models we 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. RESULTS: Low-sensitivity CRP declined, high-sensitivity CRP did not change, and IL-6 increased over time. CRP levels inversely associated with total counts of 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 low-sensitivity CRP, high-sensitivity CRP, IL-6 and a restricted measure of CRP (≤10mg/L) likely reflecting levels relevant to chronic inflammation. CONCLUSIONS: We 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.

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