Abstract Background/Introduction Inflammation has been well described in ageing older adults (inflammageing) but its association with atherogenic dyslipidaemia and biological age characterised by epigenetic age acceleration (EAA) remains poorly understood. Purpose To determine the interrelationship between inflammageing, dyslipidaemia and frailty in older adults. Methods Study participants were community-living older adults aged 60 years or above from the Undiagnosed heart Failure in frail Older individuals (UFO) cohort who were selected for this analysis in an approximate equal ratio of frailty according to the FRAIL scale (robust, pre-frail, and frail). All study participants provided written informed consent. The study was approved by the university and health network's clinical research ethics committee. Peripheral venous blood was obtained at study entry. Serum was extracted at 2–3 hours after phlebotomy and stored at -80ºC until profiling by proton (1H)-nuclear magnetic resonance (NMR) spectroscopy. DNA was isolated from centrifuged blood cells, and differentially methylated positions comprising the GrimAge2 epigenetic clock were determined using the MethylationEPIC v1.0 array. Epigenetic age of each participant was calculated using the GrimAge2 formula, and EAA was calculated as the residuals in correlation between epigenetic and chronological age. For statistical analysis of findings from 1H-NMR profiling, p-values were adjusted for multiple testing by accounting for false discovery rate (FDR). The Jonckheere-Terpstra trend test was used for analysis across frailty classes. A p-value 0.05 was considered significant. Results Among 535 older adults analysed, 186 were robust, 180 pre-frail, and 169 frail as categorised by the FRAIL scale and in line with the electronic frailty index and other frailty measurements (Table). Increasing frailty was significantly associated with EAA and a higher proportion of individuals with atherosclerotic cardiovascular disease (ASCVD) including ischaemic heart disease, myocardial infarction, and stroke (Table). 1H-NMR analysis of 31 serum lipoprotein features revealed a significant association between low-density lipoprotein (LDL) particle size (diameter) and EAA (FDR-adjusted p=0.02). Incremental frailty was found to be associated with higher serum levels of the composite 1H-NMR systemic inflammatory marker, glycosylated acetyls (GlycA; p0.0001, Fig.1A). LDL particle size was negatively correlated with GlycA (R –0.45, p0.001, Fig.1B) and frailty class (adjusted p0.0145, Fig.1C). Multiple linear regression determined that each unit increase of EAA was associated with a 0.017 mmol/L increase in GlycA (p0.0001). Conclusion(s) Systemic inflammation indicated by GlycA is increased in frail older adults and is associated with EAA and reduced LDL particle size. Further mechanistic studies are needed to clarify the pathophysiologic link between inflammageing and ASCVD.
Fung et al. (Sat,) studied this question.