Epigenetic clocks, which serve as biomarkers of biological age, have gained popularity in recent years. However, the biological mechanisms underlying these clocks remain poorly understood. This study, published in Genome Medicine, investigates the role of blood cell composition in influencing DNA methylation age and age acceleration.
What this study does not show
While the study identifies the influence of blood cell composition on DNA methylation age and age acceleration, it does not establish a direct causal relationship between these factors and specific health outcomes.
The researchers developed a principal component analysis (PCA) method that accounts for collinearity among blood cell counts. This innovative approach allows for a clearer understanding of how different cell types contribute to biological age estimations.
In their analysis of 4,058 samples, the authors found that blood cell composition could explain up to 53% of the variation in DNA methylation age. Notably, the balance between naïve and memory T cells was identified as a significant contributor. Conversely, the association between age acceleration and cell counts was weaker, explaining up to 21% of the variance, with neutrophils playing a primary role in 2nd-generation clocks.
Furthermore, the study examined the impact of cell composition on the relationship between age acceleration and 176 incident health outcomes in a larger cohort of 18,859 individuals. The findings indicated that while cell composition significantly attenuated the association of age acceleration with these health outcomes, the effect was modest.
In conclusion, the study highlights that DNA methylation age and age acceleration reflect different biological processes, with blood cell composition playing a crucial role in these associations. However, the contribution of blood cell composition to age acceleration’s association with mortality and disease outcomes appears to be limited.
Evidence scorecard
- Analytic validity: Established
- Clinical validity: Partial
- Clinical utility: Not established
The evidence is based on primary research involving human participants.