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

Stevenson, A. J.; McCartney, D. L.; Harris, S. E.; Taylor, A. M.; Redmond, P.; Starr, J. M.; Zhang, Q.; McRae, A. F.; Wray, N. R.; Spires-Jones, T. L.; McColl, B. W.; McIntosh, A. M.; Deary, I. J.; Marioni, R. E.

doi:10.1101/397877

bioRxiv · 10.1101/397877

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

Stevenson, A. J.·McCartney, D. L.·Harris, S. E.·Taylor, A. M.·Redmond, P.·Starr, J. M.·Zhang, Q.·McRae, A. F.·Wray, N. R.·Spires-Jones, T. L.·McColl, B. W.·McIntosh, A. M.·Deary, I. J.·Marioni, R. E.

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Abstract

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.\n\nMETHODSWe 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.\n\nRESULTSLow-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.\n\nCONCLUSIONSWe 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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Stevenson, A. J., McCartney, D. L., Harris, S. E., Taylor, A. M., Redmond, P., Starr, J. M., Zhang, Q., McRae, A. F., Wray, N. R., Spires-Jones, T. L., McColl, B. W., McIntosh, A. M., Deary, I. J., Marioni, R. E.. 2018-08-24. Trajectories of inflammatory biomarkers over the eighth decade and their associations with immune cell counts and epigenetic ageing. https://doi.org/10.1101/397877

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