I have written about DNA Methylation itself on my 2026 poster page here. In short it is an indication of what genes are being transcribed and links to histone acetylation, methylation and many other post translational modifications. It was found that there is a weak link between ageing and DNA methylation and also a weak link between DNA methylation and the pace of biological ageing. A lot of enthusiasm then built up for using this as a tool to measure health in the round.
I lost confidence personally in having the tests done a couple of years ago simply because they did not seem to give me any usable information as to what could be done to improve health (unlike blood biomarkers and other biomarkers). More recently there have been some research looking at the technical merits of DNA methylation tests and I will list some here.
At the bottom of this page I list four papers. The first finds that the clocks vary as to their reliability. The second finds that the value on a clock will vary depending upon the race of the individual. The third finds that professional footballers reduce their epigenetic age every time they play a match (in the 90 mins). The third that pregnancy results in an increased epigenetic age which reverses after pregnancy.
What these in the round imply is that DNA methylation is downstream of any ageing and development pointer. They also show methylation depends on a lot more things than ageing and development. My own conclusion is not to worry that much about DNA methylation itself and to study other biomarkers.
Methylation clocks fail to generalize across genetically admixed individualsFrom the abstract: "Here, we evaluate a set of first-, second-, and third-generation methylation clocks in 621 AD (Alzheimers Disease) patients and matched controls from African American, Hispanic, and White cohorts. The clocks are less accurate at predicting age in genetically admixed cohorts compared to the White cohort, especially for those with substantial African ancestry. This decreased accuracy holds in >2500 individuals of European and African ancestry from three additional datasets. The clocks also fail to consistently identify age acceleration in admixed AD cases compared to controls. "
Epigenetic Age Monitoring in Professional Soccer Players for Tracking Recovery and the Effects of Strenuous Exercise. From the abstract: "Vigorous physical activity was found to rejuvenate epigenetic clocks, with significant decreases in DNAmGrimAge2 and DNAmFitAge observed immediately after games."
The effects of pregnancy, its progression, and its cessation on human (maternal) biological aging From the abstract: "Consistent with Poganik et al.,2 we found a significant positive association between the stage of pregnancy and biological age (Figures S1A–S1E). Centering parturition as time zero, from early (−26.5 ± 2.2 weeks) to late (−8.8 ± 1.7 weeks) pregnancy, a period of approximately 18 weeks, measures of adjusted maternal biological age increased by 2.39 years for PCPhenoAge (p < 0.001, 95% CI [1.75, 3.03]), 1.19 years for PCGrimAge (p < 0.001, 95% CI [0.93, 1.46]), 2.52 years for GrimAge2 (p < 0.001, 95% CI [2.09, 2.95]), and 0.07 units for PACE (p < 0.001, 95% CI [0.05, 0.08]). We also observed a statistically significant “reversal” of biological aging across all epigenetic biomarkers from the late pregnancy to the approximately 3-month postpartum time point."
I lost confidence personally in having the tests done a couple of years ago simply because they did not seem to give me any usable information as to what could be done to improve health (unlike blood biomarkers and other biomarkers). More recently there have been some research looking at the technical merits of DNA methylation tests and I will list some here.
At the bottom of this page I list four papers. The first finds that the clocks vary as to their reliability. The second finds that the value on a clock will vary depending upon the race of the individual. The third finds that professional footballers reduce their epigenetic age every time they play a match (in the 90 mins). The third that pregnancy results in an increased epigenetic age which reverses after pregnancy.
What these in the round imply is that DNA methylation is downstream of any ageing and development pointer. They also show methylation depends on a lot more things than ageing and development. My own conclusion is not to worry that much about DNA methylation itself and to study other biomarkers.
Here are the papers:
Biological Versus Technical Reliability of Epigenetic Clocks and Implications for Disease Prognosis and Intervention Response from the abstract; "These findings highlight a critical limitation in current epigenetic clocks. Improving biological reliability will be essential for advancing their use in clinical and interventional settings."Methylation clocks fail to generalize across genetically admixed individualsFrom the abstract: "Here, we evaluate a set of first-, second-, and third-generation methylation clocks in 621 AD (Alzheimers Disease) patients and matched controls from African American, Hispanic, and White cohorts. The clocks are less accurate at predicting age in genetically admixed cohorts compared to the White cohort, especially for those with substantial African ancestry. This decreased accuracy holds in >2500 individuals of European and African ancestry from three additional datasets. The clocks also fail to consistently identify age acceleration in admixed AD cases compared to controls. "
Epigenetic Age Monitoring in Professional Soccer Players for Tracking Recovery and the Effects of Strenuous Exercise. From the abstract: "Vigorous physical activity was found to rejuvenate epigenetic clocks, with significant decreases in DNAmGrimAge2 and DNAmFitAge observed immediately after games."
The effects of pregnancy, its progression, and its cessation on human (maternal) biological aging From the abstract: "Consistent with Poganik et al.,2 we found a significant positive association between the stage of pregnancy and biological age (Figures S1A–S1E). Centering parturition as time zero, from early (−26.5 ± 2.2 weeks) to late (−8.8 ± 1.7 weeks) pregnancy, a period of approximately 18 weeks, measures of adjusted maternal biological age increased by 2.39 years for PCPhenoAge (p < 0.001, 95% CI [1.75, 3.03]), 1.19 years for PCGrimAge (p < 0.001, 95% CI [0.93, 1.46]), 2.52 years for GrimAge2 (p < 0.001, 95% CI [2.09, 2.95]), and 0.07 units for PACE (p < 0.001, 95% CI [0.05, 0.08]). We also observed a statistically significant “reversal” of biological aging across all epigenetic biomarkers from the late pregnancy to the approximately 3-month postpartum time point."
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