Occupational exposure to pesticides and epigenetic age acceleration in the Lifelines cohort study

Objective: Pesticide exposure has been implicated in age-related diseases, whereas its association with biological aging remains unclear. This study aimed to examine the association between occupational pesticide exposure and epigenetic age acceleration.
Methods: We analyzed cross-sectional data from 1,622 participants in the Dutch general population-based Lifelines cohort with available DNA methylation data. Occupational pesticide exposure and its subclasses (herbicides, insecticides, fungicides) were assessed using self-reported occupation combined with the ALOHA + job exposure matrix. Age acceleration was estimated using seven epigenetic aging measures including the Horvath, Hannum, Skin & Blood, PhenoAge, GrimAge, DunedinPACE, and DNA methylation-based telomere length (DNAmTL). Multivariable linear regression with inverse probability weighting was applied to estimate associations, adjusting for age, sex, education, income, smoking status, and co-exposure to dusts and solvents.
Results: Occupational exposure to general pesticides was associated with higher age acceleration based on the Hannum clock (β = 1.15, 95% CI: 0.18 to 2.11). The associations of the pesticide subclasses with the Hannum were all statistically significant, with the strongest observed for herbicides (β = 1.72, 95% CI: 0.69 to 2.75). No significant associations were found with second- or third-generation clocks, or with DNAmTL. Analyses restricted to current workers yielded consistent results, and herbicide exposure remained statistically significant in cumulative exposure analysis.
Conclusion: Occupational pesticide exposure was associated with accelerated epigenetic aging, most consistently captured by first-generation clocks such as the Hannum, with herbicides showing the most pronounced effect. Longitudinal occupational cohorts are warranted to confirm these associations and clarify the underlying mechanisms.
Keywords: Pesticides; Biological aging; DNA methylation