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Research Paper|Volume 17, Issue 2|pp 408—430

Exposome-wide association study of environmental chemical exposures and epigenetic aging in the national health and nutrition examination survey

Dennis Khodasevich1, Nicole Gladish1, Saher Daredia2, Anne K. Bozack1, Hanyang Shen1, Jamaji C. Nwanaji-Enwerem3,9, Belinda L. Needham4, David H. Rehkopf1,5,6,7,8, Andres Cardenas1,7
  • 1Department of Epidemiology and Population Health, Stanford University, Palo Alto, CA 94305, USA
  • 2Division of Epidemiology, Berkeley Public Health, University of California, Berkeley, Berkeley, CA 94720, USA
  • 3Department of Emergency Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
  • 4Department of Epidemiology, University of Michigan, Ann Arbor, MI 48109, USA
  • 5Department of Health Policy, Stanford University, Palo Alto, CA 94305, USA
  • 6Department of Medicine (Primary Care and Population Health), Stanford University, Palo Alto, CA 94305, USA
  • 7Department of Pediatrics, Stanford University, Palo Alto, CA 94305, USA
  • 8Department of Sociology, Stanford University, Palo Alto, CA 94305, USA
  • 9Center of Excellence in Environmental Toxicology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Received: October 16, 2024Accepted: February 3, 2025Published: February 11, 2025
https://doi.org/10.18632/aging.206201

Copyright: © 2025 Khodasevich et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Epigenetic clocks can serve as pivotal biomarkers linking environmental exposures with biological aging. However, research on the influence of environmental exposures on epigenetic aging has largely been limited to a small number of chemicals and specific populations. We harnessed data from the National Health and Nutrition Examination Survey 1999-2000 and 2001-2002 cycles to examine exposome-wide associations between environmental exposures and epigenetic aging. A total of 8 epigenetic aging biomarkers were obtained from whole blood in 2,346 participants ranging from 50-84 years of age. A total of 64 environmental exposures including phthalates, metals, pesticides, dioxins, and polychlorinated biphenyls (PCBs) were measured in blood and urine. Associations between log2-transformed/standardized exposure measures and epigenetic age acceleration (EAA) were assessed using survey-weighted generalized linear regression. A 1 standard deviation (SD) increase in log2 serum cadmium levels was associated with higher GrimAge acceleration (beta = 1.23 years, p = 3.63e-06), higher GrimAge2 acceleration (beta = 1.27 years, p = 1.62e-05), and higher DunedinPoAm (beta = 0.02, p = 2.34e-05). A 1 SD increase in log2 serum cotinine levels was associated with higher GrimAge2 acceleration (beta = 1.40 years, p = 6.53e-04) and higher DunedinPoAm (beta = 0.03, p = 6.31e-04). Associations between cadmium and EAA across several clocks persisted in sensitivity models adjusted for serum cotinine levels, and other associations involving lead, dioxins, and PCBs were identified. Several environmental exposures are associated with epigenetic aging in a nationally representative US adult population, with particularly strong associations related to cadmium and cotinine across several epigenetic clocks.