Cadmium Exposure And Age-Associated Dna Methylation Changes In Non-Smoking Women From Northern Thailand

Abstract

Introduction: Cadmium (Cd) exposure initiates cellular processes that promote aging and disrupts methylation globally. Aging is associated with DNA methylation changes, and age-associated methylation markers may serve as a biomarker of biologic age. While Cd exposure increases risk of age-related chronic diseases, we do not know if Cd mediates this effect via age-associated methylation changes. We analyzed age-associated methylation and assessed the difference between age predicted by methylation and age (Δage) in non-smoking northern Thai women exposed to Cd via environmental contamination of food. Methods: We analyzed methylation in =450,000 CpG sites in 40 non-smoking women age 40-80. We classified these women as high (HE) and low (LE) Cd exposed using a cutoff of 3 ug/L for urine Cd and matched by age within five years. We predicted methylation age (mAge) using two published methods by Horvath and Hannum et al. We analyzed differences by Cd using limma, paired t-tests, and linear mixed models. Results: Mean urine Cd was 1.0 and 16.3 ug/L in LE and HE. We identified eight age-associated differentially methylated markers in ELOV2, KLF14, PCDHB1, FHL2, FAM84B, DUSP22, and IL21R (adjusted p