Epigenetic aging during the COVID-19 pandemic: A prospective longitudinal study with prepandemic baseline data in children, adolescents, and adults

Psychosocial stress is a risk factor for aging-related diseases. The COVID-19 pandemic placed a psychosocial burden on individuals, potentially increasing the risk for aging-related diseases for which epigenetic clocks are used as early biomarkers. Based on four epigenetic clocks (DunedinPACE, GrimAge2, Horvath, and PedBE), we investigated whether epigenetic aging changed during the pandemic and whether these changes were associated with objective and subjective pandemic-related stressors and preexisting individual risk factors for poorer physical and mental health. We used prospective longitudinal data (n = 1,028), including repeated salivary DNA collection from children (n = 359, MAGE = 9.5 y), adolescents (n = 385, MAGE = 15.5 y), and adults (n = 284, MAGE = 24.3 y). Saliva was collected before the first phase of containment measures in Germany in March 2020 and after the second phase in 2021. We observed significant increases in epigenetic age acceleration (PedBE: b = 0.17, P < 0.0001; GrimAge2: b = 0.08, P < 0.0001) and pace of aging (DunedinPACE: b = 0.13, P < 0.0001) across all age groups. Prepandemic physical health and parental socioeconomic status, but not objective pandemic stressors, were significantly associated with this change. In adolescents, higher perceived pandemic burden was associated with a larger increase in pace of aging (DunedinPACE: b = 0.04, P = 0.01). Together, these findings suggest that prepandemic individual risk factors for poorer physical and mental health are accompanied by measurable increases in epigenetic aging during the COVID-19 pandemic, with adolescence representing a sensitive phase to its psychosocial burden.