Epigenetic aging acceleration among World Trade Center-exposed community members

Area of Science:

• Epigenetics
• Aging Biology
• Environmental Health

Background:

• Biological aging can accelerate beyond chronological age, influenced by environmental factors.
• Epigenetic clocks offer a method to estimate biological age and detect aging acceleration.
• World Trade Center (WTC) exposures are a known environmental stressor.

Purpose of the Study:

• To investigate if WTC exposures are associated with epigenetic aging acceleration in women.
• To assess the impact of WTC exposure on biological age using multiple epigenetic clocks.
• To examine the relationship between WTC exposure, aging acceleration, and cancer status.

Main Methods:

• Peripheral blood samples from WTC-exposed women and an unexposed reference group were analyzed.
• Epigenomes were profiled using the Infinium MethylationEPIC array.
• DNA-based epigenetic aging was estimated using Hannum, Horvath, PhenoAge, and GrimAge clocks.
• Age acceleration was calculated as the residual of epigenetic age regressed on chronological age.
• Ordinary least squares regression was used to assess the association between WTC exposure and aging acceleration.

Main Results:

• WTC exposure was significantly associated with epigenetic aging acceleration using the Hannum clock (β: 3.789, p<0.001) after adjusting for covariates.
• Similar associations were found with Horvath and PhenoAge clocks, but not GrimAge.
• Epigenetic aging acceleration linked to WTC exposure persisted when stratified by breast cancer status (β: 3.473, p<0.001) or in cancer-free participants (β: 4.369, p=0.001).
• Breast cancer diagnosis was also significantly associated with accelerated aging (β: 1.658, p=0.021).

Conclusions:

• WTC exposure is significantly associated with epigenetic aging acceleration in women.
• This association remains robust even when stratifying by cancer status.
• The findings suggest a lasting biological impact of WTC exposures on the aging process.