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

Author: Harlyn G Skinner1,2, Helena Palma-Gudiel2, James D Stewart3, Shelly-Ann Love3,4,5, Parveen Bhatti6,7,8, Aladdin H Shadyab9, Robert B Wallace10, Elena Salmoirago-Blotcher11, JoAnn E Manson12, Candyce H Kroenke13, Daniel W Belsky14,15, Yun Li16,17, Eric A Whitsel3,4, Anthony S Zannas2,16,18
Affiliation: <sup>1</sup> Center for Health Promotion and Disease Prevention, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. <sup>2</sup> Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. <sup>3</sup> Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. <sup>4</sup> Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. <sup>5</sup> Social and Scientific Systems Inc, A DLH Holdings Company, Durham, North Carolina, USA. <sup>6</sup> Cancer Control Research, British Columbia Cancer Research Institute, Vancouver, British Columbia, Canada. <sup>7</sup> School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada. <sup>8</sup> Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. <sup>9</sup> Herbert Wertheim School of Public Health and Human Longevity Science, University of California, San Diego, California, USA. <sup>10</sup> Department of Epidemiology and Internal Medicine, College of Public Health, University of Iowa, Iowa City, Iowa, USA. <sup>11</sup> Department of Medicine, Brown University School of Medicine, Providence, Rhode Island, USA. <sup>12</sup> Department of Medicine, Brigham and Women&#x27;s Hospital, Harvard Medical School, Boston, Massachusetts, USA. <sup>13</sup> Division of Research, Kaiser Permanente Northern California, Oakland, California, USA. <sup>14</sup> Department of Epidemiology, Columbia University, New York, New York, USA. <sup>15</sup> Robert N. Butler Columbia Aging Center, Columbia University, New York, New York, USA. <sup>16</sup> Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. <sup>17</sup> Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. <sup>18</sup> Carolina Stress Initiative, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Conference/Journal: J Am Geriatr Soc
Date published: 2023 Dec 27
Other: Special Notes: doi: 10.1111/jgs.18726. , Word Count: 261


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.

Keywords: aging; epigenetics; health disparities; psychosocial stress; social support.

PMID: 38149693 DOI: 10.1111/jgs.18726