Understanding biological age has become increasingly important in the field of genomics, particularly through the use of epigenetic clocks. These clocks, which are biomarkers of biological age, have been widely applied, yet their underlying biological mechanisms remain somewhat elusive. The study conducted by Jonkman et al. (2026) delves into the relationship between blood cell composition and DNA methylation age, offering new insights into how these factors interact.
What this study does not show
This study does not establish a direct causal relationship between blood cell composition and health outcomes, nor does it provide a comprehensive understanding of all factors influencing DNA methylation age.
The researchers developed a principal component analysis (PCA) method that is robust against collinearity issues often present in blood cell counts. This innovative approach allowed them to quantify the contribution of various cell types to DNA methylation age and age acceleration across a substantial dataset of 4,058 samples.
One of the key findings was that up to 53% of the variation in DNA methylation age could be attributed to the composition of blood cells, particularly the balance between naïve and memory T cells. This suggests that the immune system’s cellular makeup plays a significant role in biological aging as measured by DNA methylation.
In addition, the study examined the influence of cell composition on the association between age acceleration and 176 incident health outcomes in a larger cohort of 18,859 individuals. The results indicated that while cell counts do have an effect on age acceleration, the contribution is relatively modest, explaining up to 21% of the variance. Notably, for second-generation epigenetic clocks, this association was primarily linked to neutrophil counts.
Interestingly, the study found that the relationship between age acceleration and health outcomes was significantly attenuated when accounting for cell composition. However, this attenuation was described as modest, suggesting that while blood cell composition does influence these associations, it is not the sole factor at play.
The authors concluded that DNA methylation age (DNAmAge) and age acceleration (AgeAccel) reflect different biological processes, as evidenced by their distinct associations with blood cell composition. This distinction is crucial for understanding how biological age can be interpreted and measured, particularly in the context of health outcomes.
Evidence scorecard
- Analytic validity: Established
- Clinical validity: Not established
- Clinical utility: Not established
The evidence is based on primary research involving human samples.