Epigenetic and biological age acceleration in children with atopic dermatitis.

BACKGROUND

Atopic dermatitis (AD) 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

We sought to determine the role of epigenetic and biological aging, telomere length, and epigenetically inferred abundance of 7 inflammatory biomarkers in AD.

METHODS

We performed DNA methylation-based analyses in a pediatric AD cohort (n = 24, mean ± standard deviation [SD] age 2.56 ± 0.28 years) and age-matched healthy subjects (n = 24, age 2.09 [0.15] years) derived from blood using 5 validated algorithms that assess epigenetic age (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 AD patients for 4 algorithms: Horvath (+0.88 years; 95% confidence interval [CI], 0.33 to 1.4;  = 2.3 × 10), Skin&Blood (+0.95 years; 95% CI, 0.67 to 1.2;  = 1.8 × 10), PhenoAge (+8.2 years; 95% CI, 3.4 to 13.0;  = 1.3 × 10), and GrimAge (+1.8 years 95% CI, 0.22 to 3.3;  = .026). Moreover, patients had increased levels of β microglobulin (+47,584.4 ng/mL;  = .029), plasminogen activation inhibitor 1 (+3,432.9 ng/mL;  = 1.1 × 10), and cystatin C (+31,691 ng/mL;  = 4.0 × 10), while levels of tissue inhibitor metalloproteinase 1 (-370.7 ng/mL;  = 7.5 × 10) were decreased compared to healthy subjects.

CONCLUSION

DNA methylation changes associated with epigenetic and biological aging, and inflammatory proteins appear early in life in pediatric AD and may be relevant clinical biomarkers of pathophysiology.