Epigenetic clocks are increasingly recognized as valuable biomarkers for assessing biological age. However, the underlying biological mechanisms that drive these clocks remain poorly understood. This study, published in Genome Medicine, investigates the role of blood cell composition in influencing DNA methylation age (DNAmAge) and age acceleration (AgeAccel).
What this study does not show
While the study identifies associations between blood cell composition and epigenetic measures, it does not establish direct causal relationships or health outcomes resulting from these associations.
The researchers developed a principal component analysis (PCA) method to address the complexities of collinearity among blood cell counts. They analyzed data from 4,058 samples to quantify how much cell composition contributes to DNAmAge and AgeAccel, using six different epigenetic clocks.
Results indicated that up to 53% of the variation in DNAmAge could be attributed to blood cell counts, particularly the balance between naïve and memory T cells. In contrast, the contribution of cell composition to AgeAccel was weaker, explaining up to 21% of the variance, with neutrophils being the primary cell type involved for 2nd-generation clocks.
Furthermore, the study examined the influence of blood cell composition on the relationship between AgeAccel and 176 incident health outcomes in a larger cohort of 18,859 individuals. The findings revealed that while cell composition significantly attenuated the association between AgeAccel and health outcomes, this effect was modest.
In conclusion, the study highlights that DNAmAge and AgeAccel reflect different biological processes, with blood cell composition playing a significant role in the former but only a minor contribution to the latter’s association with mortality and disease outcomes.
Evidence scorecard
- Analytic validity: established
- Clinical validity: not established
- Clinical utility: not established
The evidence is based on primary research with human status unclassified.