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Research Paper|Volume 16, Issue 4|pp 3107—3136

Associations of prenatal one-carbon metabolism nutrients and metals with epigenetic aging biomarkers at birth and in childhood in a US cohort

Anne K. Bozack1, Sheryl L. Rifas-Shiman2, Andrea A. Baccarelli3, Robert O. Wright4, Diane R. Gold5, Emily Oken2, Marie-France Hivert2, Andres Cardenas6
  • 1Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, CA 94305, USA
  • 2Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA 02215, USA
  • 3Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York City, NY 10032, USA
  • 4Department of Environmental Medicine and Institute for Exposomic Research, Icahn School of Medicine at Mount Sinai, New York City, NY 10029, USA
  • 5Department of Environmental Health, Harvard T.H. Chan School of Public Health, Harvard University, Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
  • 6Department of Epidemiology and Population Health and Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA
Received: October 31, 2023Accepted: January 29, 2024Published: February 26, 2024
https://doi.org/10.18632/aging.205602

Copyright: © 2024 Bozack 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 gestational age acceleration (EGAA) at birth and epigenetic age acceleration (EAA) in childhood may be biomarkers of the intrauterine environment. We investigated the extent to which first-trimester folate, B12, 5 essential, and 7 non-essential metals in maternal circulation are associated with EGAA and EAA in early life. Bohlin EGAA and Horvath pan-tissue and skin and blood EAA were calculated using DNA methylation measured in cord blood (N=351) and mid-childhood blood (N=326; median age = 7.7 years) in the Project Viva pre-birth cohort. A one standard deviation increase in individual essential metals (copper, manganese, and zinc) was associated with 0.94-1.2 weeks lower Horvath EAA at birth, and patterns of exposures identified by exploratory factor analysis suggested that a common source of essential metals was associated with Horvath EAA. We also observed evidence nonlinear associations of zinc with Bohlin EGAA, magnesium and lead with Horvath EAA, and cesium with skin and blood EAA at birth. Overall, associations at birth did not persist in mid-childhood; however, arsenic was associated with greater EAA at birth and in childhood. Prenatal metals, including essential metals and arsenic, are associated with epigenetic aging in early life, which might be associated with future health.