The study published in Genome Medicine investigates the relationship between blood cell composition and DNA methylation age, a biomarker often used to estimate biological age. The authors, Jonkman et al., highlight that while epigenetic clocks are widely used, their biological foundations are not fully understood. This research aims to clarify the role of blood cell types in influencing these epigenetic measures.
What this study does not show
While the study identifies associations between blood cell composition and DNA methylation metrics, it does not establish direct causal relationships or provide evidence of improved health outcomes based on these findings.
The authors developed a principal component analysis (PCA) method that effectively addresses collinearity issues among blood cell counts. They analyzed data from 4,058 samples to quantify how much cell composition contributes to DNA methylation age and age acceleration, as estimated by various epigenetic clocks.
Results indicate that up to 53% of the variation in DNA methylation age can be attributed to blood cell counts, particularly the balance between naïve and memory T cells. In contrast, the association of age acceleration with cell counts explains up to 21% of the variance, with neutrophils playing a significant role in 2nd-generation clocks.
Furthermore, the study tested the influence of cell composition on the relationship between age acceleration and 176 health outcomes in a larger cohort of 18,859 individuals. The findings suggest that while cell composition does attenuate the association between age acceleration and health outcomes, the effect is modest.
The authors conclude that DNA methylation age and age acceleration reflect different biological processes, as evidenced by their distinct associations with blood cell composition. Notably, the contribution of blood cell composition to age acceleration’s association with mortality and disease outcomes appears to be minor.
Evidence scorecard
- Analytic validity: Established
- Clinical validity: Not established
- Clinical utility: Not established
This evidence is based on primary research findings.