Epigenetic age acceleration is associated with allergy and asthma in children in Project Viva

Background Epigeneticclocks have been suggested to capture one feature of the complexity between aging and the epigenome. However, little is known about the epigeneticclock in childhood allergyand asthma. Objective We sought to examine associations of DNA methylation age (DNAmAge) and epigeneticage acceleration with childhood allergyand asthma. Methods We calculated DNAmAge and age acceleration at birth, early childhood, and midchildhood based on the IlluminaHumanMethylation450BeadChip in Project Viva. We evaluated epigeneticclock associations with allergyand asthma using covariate-adjusted linear and logistic regressions. We attempted to replicate our findings in the Genetics of Asthma in Costa Rica Study. Results At midchildhood (mean age, 7.8 years) in Project Viva, DNAmAge and age acceleration were cross-sectionally associated with greater total serum IgE levels and greater odds of atopic sensitization. Every 1-year increase in intrinsic epigeneticage acceleration was associated with a 1.22 (95% CI, 1.07-1.39), 1.17 (95% CI, 1.03-1.34), and 1.29 (95% CI, 1.12-1.49) greater odds of atopic sensitization and environmental and food allergensensitization. DNAmAge and extrinsic epigeneticage acceleration were also cross-sectionally associated with current asthma at midchildhood. DNAmAge and age acceleration at birth and early childhood were not associated with midchildhood allergyor asthma. The midchildhood association between age acceleration and atopic sensitization were replicated in an independent data set. Conclusions Because the epigeneticclock might reflect immune and developmental components of biological aging, our study suggests pathways through which molecular epigeneticmechanisms of immunity, development, and maturation can interact along the age axis and associate with childhood allergyand asthma by midchildhood.