Associations of epigenetic aging and COVID-19: a 3-year longitudinal study

Aging and COVID-19 are known to influence DNA methylation, potentially affecting the rate of aging and the risk of disease. The physiological functions of 54 volunteers—including maximal oxygen uptake (VO₂ max), grip strength, and vertical jump—were assessed just before the COVID-19 pandemic and again three years later. Of these volunteers, 27 had contracted COVID-19. Eight epigenetic clocks were used to assess the rate of aging during the three-year period: DNAmAge showed accelerated aging and five clocks showed slowed aging (DNAmAgeSkinBlood, DNAmAgeHannum, DNAmFitAge, PhenoAge, and DNAmTL). When we considered only females, we observed a stronger effect in the increase of DNAmAge acceleration, while we observed slowed aging in the case of SkinBloodClock, and DNAmTL. The methylation of the promoter region of the H1FNT genes, which encodes testis-specific histone H1 family member N (H1fnt) and plays a crucial role in spermatogenesis decreased the most significantly. In contrast, the promoter of CSTL1, which encodes Cystatin-like 1, showed the most significant increase. We found that having COVID-19 during the 3-year study period significantly increased the progress of aging assessed by DNAmGrimAge, DNAmGrimAge2, and DNAmFitAge (p=0.024, 0.047, 0.032, respectively after we adjusted the analysis for baseline variables). The data suggest that COVID-19 may have a mild long-term effect on epigenetic aging. 54 adult volunteers were assessed at two-time points: before the COVID-19 pandemic (2019) and three years later (2022-2023). Among them, 27 individuals contracted COVID-19, while 27 remained uninfected. The dataset includes DNA methylation profiles from blood samples, physiological function measurements (VO₂ max, grip strength, vertical jump), and metadata covering age, sex, COVID-19 status, and baseline health variables. DNA methylation analysis was performed using the Illumina EPIC array. Due to patient privacy concerns, raw data idat files could not be provided.