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

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.