Association of blood cadmium levels with epigenetic age acceleration in U.S. adults aged > 50 years.

DNA methylation (DNAm) is a sensitive biomarker of aging-related processes, and novel epigenetic-based "clocks" can estimate accelerated biological aging. Cadmium (Cd) can alter cellular processes that promote aging and disrupt global methylation patterns. However, few studies have investigated the association between blood Cd and accelerated aging. We aimed to investigate the association between blood Cd and four DNAm-based epigenetic age accelerations in individuals over 50 in the United States, using data from the National Health and Nutrition Examination Survey (NHANES). DNAm-epigenetic biomarkers and blood Cd data from the NHANES database (1999-2002) were retrieved for this study. We evaluated four epigenetic ages: HorvathAge, HannumAge, PhenoAge, and GrimAge. Age acceleration was calculated by extracting the residuals from the regression of chronological age on each epigenetic age measure. We used weighted linear regression models and subgroup analyses to investigate the associations between blood Cd levels and these age accelerations, adjusting for potential confounding factors. Higher blood Cd levels (≥0.5 μg/dl) were significantly associated with increased age acceleration for PhenoAge (β = 1.37, P = 0.017) and GrimAge (β = 1.31, P = 0.003) in adjusted models. A significant association was also observed for HannumAge (β = 0.94, P = 0.016), although this association was not significant for continuous Cd levels (P = 0.111). No significant associations were found for HorvathAge. Subgroup analyses indicated consistent associations across demographic and lifestyle subgroups, with no significant interactions. In this study, after adjusting for confounders, blood Cd levels were positively associated with PhenoAge acceleration and GrimAge acceleration in people over 50 in the United States. These results may be useful in proposing interventions in environmental exposures to slow the aging process and prevent age-related diseases.