Epigenetics-Based Age Acceleration Associated with 2,3,7,8 TCDD Exposure in Older Americans
Baek-Yong Choi1, Seung-Woo Ryoo1, Seok-Yoon Son1
1Department of Preventive Medicine, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
International Journal of Molecular Sciences
|February 26, 2025
Summary
Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is linked to accelerated epigenetic aging in older adults. This toxic chemical impacts DNA methylation clocks, particularly those related to mortality, in a dose-dependent manner.
Area of Science:
- Environmental Health
- Toxicology
- Epigenetics
Background:
- 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a highly toxic environmental pollutant with known adverse health effects.
- Previous research suggests TCDD exposure may influence aging markers like telomere length and sperm DNA methylation age.
- The specific relationship between TCDD and broader epigenetic aging in humans remains under-investigated.
Purpose of the Study:
- To investigate the association between serum TCDD levels and multiple DNA methylation-based epigenetic clocks in older adults.
- To determine if TCDD exposure correlates with accelerated biological aging as measured by epigenetic clocks.
- To explore potential dose-dependent and non-linear relationships between TCDD and epigenetic aging.
Main Methods:
- Analysis of data from 589 older adults (aged 50-79) from the 1999-2002 National Health and Nutrition Examination Survey.
- Measurement of serum TCDD levels using high-resolution gas chromatography/isotope-dilution high-resolution mass spectrometry.
- Assessment of six DNA methylation-based epigenetic clocks (Horvath Age, Hannum Age, SkinBlood Age, Pheno Age, Grim Age, Grim Age2) using whole blood DNA methylation data.
Main Results:
- Significant associations were found between TCDD levels and several epigenetic clocks (Horvath Age, Hannum Age, Pheno Age, Grim Age, Grim Age2).
- After lipid adjustment, significant associations persisted for PhenoAge and Grim Age2.
- Non-linear trends, suggesting a threshold effect, were most pronounced for PhenoAge, Grim Age, and Grim Age2.
Conclusions:
- TCDD exposure is associated with accelerated epigenetic aging in older adults.
- The impact of TCDD on epigenetic aging, particularly on mortality-related clocks, appears to be dose-dependent and non-linear.
- These findings highlight the potential of TCDD as an environmental factor influencing the aging process through epigenetic mechanisms.
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