Volume 72, Issue 2 p. 349-360
CLINICAL INVESTIGATION

Stressful life events, social support, and epigenetic aging in the Women's Health Initiative

Harlyn G. Skinner PhD

Harlyn G. Skinner PhD

Center for Health Promotion and Disease Prevention, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

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Helena Palma-Gudiel PhD

Helena Palma-Gudiel PhD

Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

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James D. Stewart MA

James D. Stewart MA

Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

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Shelly-Ann Love PhD

Shelly-Ann Love PhD

Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

Social and Scientific Systems Inc, A DLH Holdings Company, Durham, North Carolina, USA

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Parveen Bhatti PhD

Parveen Bhatti PhD

Cancer Control Research, British Columbia Cancer Research Institute, Vancouver, British Columbia, Canada

School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada

Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

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Aladdin H. Shadyab PhD

Aladdin H. Shadyab PhD

Herbert Wertheim School of Public Health and Human Longevity Science, University of California, San Diego, California, USA

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Robert B. Wallace MD

Robert B. Wallace MD

Department of Epidemiology and Internal Medicine, College of Public Health, University of Iowa, Iowa City, Iowa, USA

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Elena Salmoirago-Blotcher MD

Elena Salmoirago-Blotcher MD

Department of Medicine, Brown University School of Medicine, Providence, Rhode Island, USA

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JoAnn E. Manson MD

JoAnn E. Manson MD

Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA

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Candyce H. Kroenke ScD

Candyce H. Kroenke ScD

Division of Research, Kaiser Permanente Northern California, Oakland, California, USA

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Daniel W. Belsky PhD

Daniel W. Belsky PhD

Department of Epidemiology, Columbia University, New York, New York, USA

Robert N. Butler Columbia Aging Center, Columbia University, New York, New York, USA

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Yun Li PhD

Yun Li PhD

Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

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Eric A. Whitsel MD

Eric A. Whitsel MD

Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

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Anthony S. Zannas PhD

Corresponding Author

Anthony S. Zannas PhD

Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

Carolina Stress Initiative, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

Correspondence

Anthony S. Zannas, Department of Psychiatry, University of North Carolina at Chapel Hill, 438 Taylor Hall, 109 Mason Farm Road, Chapel Hill, NC, USA.

Email: [email protected]

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First published: 27 December 2023

Abstract

Background

Elevated psychosocial stress has been linked with accelerated biological aging, including composite DNA methylation (DNAm) markers that predict aging-related outcomes (“epigenetic age”). However, no study has examined whether stressful life events (SLEs) are associated with epigenetic age acceleration in postmenopausal women, an aging population characterized by increased stress burden and disease risk.

Methods

We leveraged the Women's Health Initiative, a large muti-ancestry cohort of postmenopausal women with available psychosocial stress measures over the past year and epigenomic data. SLEs and social support were ascertained via self-report questionnaires. Whole blood DNAm array (450 K) data were used to calculate five DNAm-based predictors of chronological age, health span and life span, and telomere length (HorvathAge, HannumAge, PhenoAge, GrimAge, DNAmTL).

Results

After controlling for potential confounders, higher SLE burden was significantly associated with accelerated epigenetic aging, as measured by GrimAge (β: 0.34, 95% CI: 0.08, 0.59) and DNAmTL (β: −0.016, 95% CI: −0.028, −0.004). Exploratory analyses showed that SLEs-GrimAge associations were stronger in Black women as compared to other races/ethnicities and in those with lower social support levels. In women with lower social support, SLEs-DNAmTL associations showed opposite association in Hispanic women as compared to other race/ethnicity groups.

Conclusions

Our findings suggest that elevated stress burden is associated with accelerated epigenetic aging in postmenopausal women. Lower social support and/or self-reported race/ethnicity may modify the association of stress with epigenetic age acceleration. These findings advance understanding of how stress may contribute to aging-related outcomes and have important implications for disease prevention and treatment in aging women.

CONFLICT OF INTEREST STATEMENT

The authors have no relevant conflicts to declare.