A Review of the Epigenetic Clock: Emerging Biomarkers for Asthma and Allergic Disease

Abstract

DNA methylation (DNAm) is a dynamic, age-dependent epigenetic modification that can be used to study interactions between genetic and environmental factors. Environmental exposures during critical periods of growth and development may alter DNAm patterns, leading to increased susceptibility to diseases such as asthma and allergies. One method to study the role of DNAm is the epigenetic clock—an algorithm that uses DNAm levels at select age-informative Cytosine-phosphate-Guanine (CpG) dinucleotides to predict epigenetic age (EA). The difference between EA and calendar age (CA) is termed epigenetic age acceleration (EAA) and reveals information about the biological capacity of an individual. Associations between EAA and disease susceptibility have been demonstrated for a variety of age-related conditions and, more recently, phenotypes such as asthma and allergic diseases, which often begin in childhood and progress throughout the lifespan. In this review, we explore different epigenetic clocks and how they have been applied, particularly as related to childhood asthma. We delve into how in utero and early life exposures (e.g., smoking, air pollution, maternal BMI) result in methylation changes. Furthermore, we explore the potential for EAA to be used as a biomarker for asthma and allergic diseases and identify areas for further study.

Climate Change and New Challenges for Rural Communities: Particulate Matter Matters

“…Epigenetic alterations have been attributed to many diseases. Indeed, altered DNA methylation-one of the major epigenetic mechanisms of control over the proper expression of genetic information-has been reported in many diseases, including respiratory disease (i.e., asthma) and cancer [34,35]. Accumulating evidence indicates that epigenetic reprogramming is not only a consequence of disease but often serves as a driving mechanism in the pathogenesis of diseases [36].…”

Sex-Specific Associations between Prenatal Exposure to Di(2-ethylhexyl) Phthalate, Epigenetic Age Acceleration, and Susceptibility to Early Childhood Upper Respiratory Infections

“…Epigenetic age acceleration (EAA) as estimated by the Horvath clock has been robustly associated with both early life exposures and later life morbidity and mortality [45], including respiratory illness outcomes [46]. EAA has also been consistently associated with, and even hailed as an emerging biomarker of asthma and atopic diseases in children [47,48] and may provide insight into the biological embedding of early life chemical exposures on immune system development. For example, one study found that accelerated epigenetic age in children was associated both with an increase in allergy and serum IgE [47], an antibody involved in allergic response mechanisms, which has also previously been found to increase with higher prenatal exposure to phthalates [32].…”