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Research Paper|Volume 17, Issue 11|pp 2759—2777

Epigenetic age predicts depressive symptoms during the COVID-19 pandemic in the Canadian Longitudinal Study on Aging: importance of biological sex

Cindy K. Barha1,2,3,4, Teresa Liu-Ambrose3,4, Amy M. Inkster5,6, Ryan S. Falck3,4,7, Joel S. Burma1,2, Susan Kirkland8, Lauren E. Griffith9,10, Mary Thompson11, Nicole E. Basta12, Jacqueline M. McMillan13, Cynthia Balion14, Christina Wolfson12, Parminder Raina9,10, on behalf of the Canadian Longitudinal Study on Aging (CLSA) Team
  • 1Barha Brain Health Laboratory, Faculty of Kinesiology, University of Calgary, Alberta, Canada
  • 2Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada
  • 3Aging, Mobility, and Cognitive Neuroscience Laboratory, Department of Physical Therapy, University of British Columbia, Vancouver, BC, Canada
  • 4Djavad Mowafaghian Centre for Brain Health, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
  • 5Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada
  • 6BC Children’s Hospital Research Institute, Vancouver, BC, Canada
  • 7School of Biomedical Engineering, University of British Columbia, Vancouver, BC, Canada
  • 8Department of Community Health and Epidemiology, Dalhousie University, Halifax, Nova Scotia, Canada
  • 9Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada
  • 10McMaster Institute for Research on Aging, McMaster University, Hamilton, ON, Canada
  • 11Department of Statistics and Actuarial Science, University of Waterloo, Waterloo, ON, Canada
  • 12Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada
  • 13Division of Geriatric Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
  • 14Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada
Received: May 12, 2025Accepted: October 30, 2025Published: November 18, 2025

Copyright: © 2025 Barha 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 age is a biological metric of overall health and may predict mental health responses to unprecedented stressors. We sought to determine whether epigenetic age acceleration can predict older adults’ trajectory of depressive symptoms before and during the COVID-19 pandemic, and whether sex differences exist.

Data from baseline (2012-2015), first follow-up (2015-2018), and COVID-19 Baseline survey (April-May 2020) and COVID-19 Exit survey (September-December 2020) of the Canadian Longitudinal Study on Aging were used. Epigenetic age was measured at the study baseline, and depressive symptoms were assessed at each of the four time points using the 10-item Center for Epidemiological Studies Depression Scale (CESD-10). Sex-stratified mixed linear models examined the effect of epigenetic age (measured by DNAmAge and Hannum Age) on changes in CESD-10.

The mean participant chronological age at study entry was 63±10 years (46% female). Unexpectedly, younger epigenetic age predicted increases in depressive symptoms from first follow-up to COVID-19 Baseline survey (p’s < 0.05) in females only. Higher epigenetic age was not related to changes in CES-10 score during that time period (p’s > 0.05).

These findings suggest epigenetic age is a biological factor that can identify females at risk for greater negative effects of major life stressors on mental health.