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

Environ Res. 2026 Jan 15:289:123371. doi: 10.1016/j.envres.2025.123371. Epub 2025 Nov 19.

Abstract

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 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.

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 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.

Keywords: Biological aging; DNA methylation; Pesticides.

MeSH terms

  • Adult
  • Aged
  • Aging* / drug effects
  • Aging* / genetics
  • Cohort Studies
  • Cross-Sectional Studies
  • DNA Methylation / drug effects
  • Epigenesis, Genetic* / drug effects
  • Female
  • Humans
  • Male
  • Middle Aged
  • Netherlands
  • Occupational Exposure* / adverse effects
  • Pesticides* / toxicity

Substances

  • Pesticides