Validity and cardio-metabolic risk profiles of DNA methylation clocks among adults in south-central Côte d’Ivoire

Abstract

Abstract Background Aging populations in Africa face a growing burden of non-communicable diseases (NCDs), contextualized in broad external exposome and weak health systems. These could accelerate aging and shorten lifespan. DNA methylation (DNAm) epigenetic clocks allow investigation of biological aging, and perform well in high-income countries. However, their validity has rarely been tested in low- and middle-income countries. We investigated the performance of epigenetic clocks (as aging biomarkers), and their cardio-metabolic risk profiles among adults in south-central Côte d’Ivoire. Results We derived four measures of epigenetic clocks (i.e., HorvathAge, HannumAge, PhenoAge and GrimAge) and their corresponding epigenetic age acceleration (EAA; Intrinsic, Extrinsic, PhenoAA and GrimAA) using genome-wide DNAm data from 393 participants of the Côte d’Ivoire dual burden of disease study, aged 18–79 years. Epigenetic age exhibited strong correlations (0.83 ≤ Pearson’s r ≤ 0.93) but weaker concordance (0.73 ≤ Lin’s rC ≤ 0.85) with chronological age. Epigenetic clocks optimally predicted chronological age at 32 (HannumAge), 62 (HorvathAge) and 78 (GrimAge) years. Multivariable linear EAA models identified male sex (IEAA, EEAA and GrimAA), lower household wealth (EEAA and PhenoAA), high-risk alcohol intake (PhenoAA and GrimAA), smoking (GrimAA), physical activity (IEAA and GrimAA) and body mass index [BMI] (GrimAA) as independent determinants. Physical activity and BMI exhibited quadratic associations with GrimAA. Illustratively, GrimAge was accelerated in underweight and obese participants. Risk associations of GrimAA were largely driven by age-adjusted DNAm surrogate plasminogen activator inhibitor-1 (DNAmPAI-1) and pack years. Multivariable logistic models of cardio-metabolic phenotypes identified EEAA, PhenoAA and DNAmPAI-1 as determinants of high blood pressure, fasting glucose, triglycerides and metabolic syndrome severity. Conclusions We provide evidence validating the applicability of epigenetic clocks as aging biomarkers and potential link between sociodemographic and lifestyle-related factors, and cardio-metabolic health in the underrepresented African population. Future longitudinal studies incorporating broad environmental aspects and age-related clinical outcomes should allow to pinpoint the clinical and public health utility of DNAm clocks as mediators in NCD trajectory, in low- and middle-income countries.