Epigenetic and biological age acceleration in children with atopic dermatitis

Richie Jeremian; Alexandra Malinowski; Edward S Oh; Melinda Gooderham; Cathryn Sibbald; Jensen Yeung; Yuka Asai; Vincent Piguet; Carolyn S Jack

doi:10.1016/j.jacig.2024.100275

Epigenetic and biological age acceleration in children with atopic dermatitis

J Allergy Clin Immunol Glob. 2024 May 3;3(3):100275. doi: 10.1016/j.jacig.2024.100275. eCollection 2024 Aug.

Authors

Richie Jeremian^{1

2}, Alexandra Malinowski³, Edward S Oh³, Melinda Gooderham⁴, Cathryn Sibbald⁵, Jensen Yeung⁶, Yuka Asai⁷, Vincent Piguet^{6

8}, Carolyn S Jack^{1

2}

Affiliations

¹ Faculty of Medicine & Health Sciences, McGill University, Montreal, Quebec, Canada.
² McGill University Health Centre (MUHC) Center of Excellence for Atopic Dermatitis, Montreal, Quebec, Canada.
³ Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
⁴ SKiN Centre for Dermatology, Peterborough, Probity Medical Research, Waterloo; and Queen's University, Kingston, Ontario, Canada.
⁵ Department of Paediatrics, Division of Dermatology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
⁶ Department of Medicine, Division of Dermatology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
⁷ Division of Dermatology, School of Medicine, Faculty of Health Sciences, Queen's University, Kingston, Ontario, Canada.
⁸ Department of Medicine, Division of Dermatology, Women's College Hospital, Toronto, Ontario, Canada.

Abstract

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; P = 2.3 × 10^-3), Skin&Blood (+0.95 years; 95% CI, 0.67 to 1.2; P = 1.8 × 10^-8), PhenoAge (+8.2 years; 95% CI, 3.4 to 13.0; P = 1.3 × 10^-3), and GrimAge (+1.8 years 95% CI, 0.22 to 3.3; P = .026). Moreover, patients had increased levels of β₂ microglobulin (+47,584.4 ng/mL; P = .029), plasminogen activation inhibitor 1 (+3,432.9 ng/mL; P = 1.1 × 10^-5), and cystatin C (+31,691 ng/mL; P = 4.0 × 10^-5), while levels of tissue inhibitor metalloproteinase 1 (-370.7 ng/mL; P = 7.5 × 10^-4) 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.

Keywords: Atopic dermatitis; DNA methylation; biological aging; epigenetic aging; inflammatory biomarkers.