Epigenetic entropy, social disparity, and health and lifespan in the Women’s Health Initiative

Khyobeni Mozhui; Athena Starlard-Davenport; Yangbo Sun; Aladdin H. Shadyab; Ramon Casanova; Fridtjof Thomas; Robert B Wallace; Jay H Fowke; Karen C Johnson

doi:10.1101/2025.02.21.25322696

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Epigenetic entropy, social disparity, and health and lifespan in the Women’s Health Initiative

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Epigenetic entropy, social disparity, and health and lifespan in the Women’s Health Initiative

Khyobeni Mozhui, Athena Starlard-Davenport, Yangbo Sun, Aladdin H. Shadyab, Ramon Casanova, Fridtjof Thomas, Robert B Wallace, Jay H Fowke and Karen C Johnson

medRxiv

Cold Spring Harbor Laboratory Press, 1.2

02/26/2025

DOI: 10.1101/2025.02.21.25322696

PMCID: PMC11888519

PMID: 40061325

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https://doi.org/10.1101/2025.02.21.25322696View

Preprint (Author's original)This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

The pace of aging varies between individuals and is marked by changes in DNA methylation (DNAm) including an increase in randomness or entropy. Here, we computed epigenetic scores of aging and entropy using DNAm datasets from the Women’s Health Initiative (WHI). We investigated how different epigenetic aging metrics relate to demographic and health variables, and mortality risk. Income and education, two proxies of socioeconomics (SE), had consistent associations with epigenetic aging and entropy. Notably, stochastic increases in DNAm at sites targeted by the polycomb proteins were significantly related to both aging and SE. While higher income was associated with reduced age-related DNAm changes in White women, the protective effect of income was diminished in Black and Hispanic women, and on average, Black and Hispanic women had relatively more aged epigenomes. Faster pace of aging, as estimated by the DunedinPACE, predicted higher mortality risk, while the maintenance of methylation at enhancer regions was associated with improved survival. Our findings demonstrate close ties between social and economic factors and aspects of epigenetic aging, suggesting potential biological mechanisms through which societal disparities may contribute to differences in health outcomes and lifespan across demographic groups.

Epidemiology

Details

Title: Subtitle: Epigenetic entropy, social disparity, and health and lifespan in the Women’s Health Initiative
Creators: Khyobeni Mozhui - University of Tennessee Health Science Center
Athena Starlard-Davenport - University of Tennessee Health Science Center
Yangbo Sun - University of Tennessee Health Science Center
Aladdin H. Shadyab - University of California San Diego
Ramon Casanova - Wake Forest University
Fridtjof Thomas - University of Tennessee Health Science Center
Robert B Wallace - University of Iowa
Jay H Fowke - University of Tennessee Health Science Center
Karen C Johnson - University of Tennessee Health Science Center
Resource Type: Preprint
Publication Details: medRxiv
Edition: 1.2
DOI: 10.1101/2025.02.21.25322696
PMID: 40061325
PMCID: PMC11888519
Publisher: Cold Spring Harbor Laboratory Press
Number of pages: 41
Language: English
Date posted: 02/26/2025
Academic Unit: Epidemiology; Injury Prevention Research Center
Record Identifier: 9984800201402771

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