The study published in Genome Medicine investigates the relationship between blood cell composition and DNA methylation age, a biomarker often used to assess biological aging. The authors highlight that while epigenetic clocks are widely utilized, their biological mechanisms remain poorly understood. Previous research indicated that the proportions of naïve and memory T cells could influence these clocks, prompting further exploration into blood cell composition as a potential factor.
Methods
The researchers developed a principal component analysis (PCA) method that effectively addresses the collinearity of blood cell counts. This method was applied to analyze 4,058 samples, quantifying the contribution of cell composition to DNA methylation age and age acceleration as estimated by various epigenetic clocks. Additionally, the study examined the impact of cell composition on the relationship between age acceleration and 176 health outcomes using data from 18,859 individuals.
Results
Findings revealed that up to 53% of the variation in DNA methylation age could be attributed to blood cell counts, particularly influenced by the balance of naïve and memory T cells. In contrast, the association between age acceleration and cell counts explained a maximum of 21% of the variance, with neutrophils being the primary contributor for 2nd-generation clocks. The study also validated these findings through artificial cell mixtures.
Interestingly, while cell composition significantly attenuated the association of age acceleration with the 176 health outcomes investigated, the effect was described as modest. This suggests that although blood cell composition plays a role in the biological interpretation of age acceleration, it only minimally contributes to its association with mortality and disease outcomes.
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 imply that modifying blood cell composition will influence DNA methylation age or age acceleration.
Evidence scorecard
- Analytic validity: established
- Clinical validity: not established
- Clinical utility: not established
The evidence is based on primary research involving human samples.