Epigenetic and biological age acceleration in a pediatric cohort of atopic dermatitis

Background Atopic dermatitis is a chronic inflammatory skin disease resulting from the complex interplay of genetic and environmental factors, meriting exploration using temporally-dynamic biomarkers. DNA methylation-based algorithms have been trained to accurately estimate biological age, and deviation of predicted age from true age (epigenetic age acceleration) has been implicated in several inflammatory diseases, including asthma. Objective To determine the role of epigenetic and biological aging, telomere length, and epigenetically-inferred abundance of seven inflammatory biomarkers in atopic dermatitis. Methods We performed DNA methylation-based analyses in a pediatric atopic dermatitis cohort (n=24, mean age 2.56±0.28y) and age-matched healthy subjects (n=24, mean age 2.09±0.15y) derived from blood, using five validated algorithms that assess epigenetic (Horvath, Skin&Blood) and biological age (PhenoAge, GrimAge), telomere length (TelomereLength), and inflammatory biomarker levels. Results Epigenetic and biological age, but not telomere length, were accelerated in atopic dermatitis patients for four algorithms: Horvath (+0.88 years; 95%CI 0.33-1.4; p=2.3x10-3), Skin&Blood (+0.95 years; 95%CI 0.67-1.2; p=1.8x10-8), PhenoAge (+8.2 years; 95%CI 3.4-13.0; p=1.3x10-3), and GrimAge (+1.8 years 95%CI 0.22-3.3; p=0.026). Moreover, patients had increased levels of beta-2-microglobulin (+47,584.4 ng/ml; p=0.029), plasminogen activation inhibitor 1 (+3,432.9 ng/ml; p=1.1x10-5) and cystatin C (+31,691 ng/ml; p=4.0x10-5), while levels of tissue inhibitor metalloproteinase 1 (-370.7 ng/ml; p=7.5x10-4) were decreased versus healthy subjects. Conclusion DNA methylation changes associated with epigenetic and biological aging, and inflammatory proteins appear early in life in pediatric atopic dermatitis and may be relevant clinical biomarkers of pathophysiology.