Early-life exposure to secondhand smoke and polycyclic aromatic hydrocarbons: associations with epigenetic aging...

Epigenetic clocks are valuable tools for assessing biological age. Exposure to secondhand smoke (SHS) and polycyclic aromatic hydrocarbons (PAHs) has been linked with epigenetic age deviation (EAD) in adults. However, associations in children remain largely unexplored. We investigated relationships between exposure-spanning prenatal, early postnatal, current (36-60 months, time of sample collection) periods-and EAD in preschool-aged children. DNA methylation was measured in buccal cells from 43 children (mean age: 4.1 years) in the CAries Risk from exposure to Environmental tobacco Smoke-Household Air Pollution Intervention Network cohort. SHS exposure was assessed using urinary cotinine and 3-hydroxycotinine (3-HC), while PAHs exposure was assessed via urinary 2-naphthol (2-NAP) and 1-hydroxypyrene (1-PYR). Nicotine equivalents were calculated as molar sum of cotinine + 3-HC. EAD was estimated using Horvath, Skin&Blood, Pediatric Buccal Epigenetic (PedBE), and DNA methylation-based telomere length (DNAmTL) clocks. Associations between exposures and EAD were evaluated using linear regression, adjusting for study site, mother's education, child's body mass index z-score, age, and sex. Chronological age significantly correlated with all epigenetic clocks (r = 0.37-0.78) and with DNAmTL estimator (r = -0.38). Current SHS exposure, as measured by urinary cotinine, was associated with Horvath EAD (B = 0.23 years, P = .05). Similarly, current 3-HC and nicotine equivalents were positively associated with PedBE EAD (B = 0.08 years, P = .04; B = 0.11 years, P = .05, respectively). Among PAH metabolites, current 2-NAP levels were associated with principal component-based Skin&Blood EAD (B = 0.21 years, P = .02) and PedBE EAD (B = 0.13 years, P = .05). Findings suggest early-life SHS and PAHs exposure may contribute to accelerated epigenetic aging in children.