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

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.

We analyzed cross-sectional data from 1622 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.

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.

Occupational pesticide exposure was consistently associated with accelerated epigenetic aging, as measured 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.