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

Abstract

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 3 years later. Of these volunteers, 27 had contracted COVID- 19. Eight epigenetic clocks were used to assess the rate of aging during the 3-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 H1 FNT 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.

Keywords: COVID- 19; Epigenetic aging; Epigenetic clocks; H1 FNT; Longitudinal aging.

Fig. 1

Increased physical fitness of middle-aged and older individuals during the COVID- 19 pandemic except for SARS-CoV- 2 infected ones. a Maximal relative oxygen uptake (VO2 max), maximum vertical jump (Max Jump), and maximum handgrip force (Max Grip) measured just before the COVID- 19 pandemic (Before COVID) and 3 years later during the COVID- 19 pandemic (COVID). All participants are included (n = 54) regardless of the infection status. b The same analysis with the separation of genders (females and males). c The same analysis with the separation by SARS-CoV- 2 infection status (infected and non-infected). d Comparison of the 3-year-change of fitness for infected and non-infected groups

Fig. 2

Mixed changes of epigenetic aging in middle-aged and older individuals during the COVID- 19 pandemic. a Age acceleration of eight aging clocks (DNAmAge, DNAmAgeHannum, DNAmAgeSkinBloodClock, DNAmFitAge, PhenoAge, DNAmTL, DNAmGrimAge, and DNAmGrimAge2) measured just before the COVID- 19 pandemic (Before COVID) and 3 years later during the COVID- 19 pandemic (COVID). All participants are included regardless of the infection status. b The same analysis with the separation of genders (females and males). c The same analysis for subjects who were not infected by SARS-CoV- 2 during the examined 3-year period (non-infected). d The same analysis for subjects who were infected by SARS-CoV- 2 during the examined 3-year period (infected)

Fig. 3

Association of SARS-COV- 2 infection DNA methylation-based aging clock. a We directly compared the DNA methylation-based age acceleration changes of SARS-CoV- 2 infected and non-infected individuals during the examined 3-year-period. We examined eight aging clocks. b The same analysis with the separation of genders (females and males)