In recent research published in Genome Medicine, the authors investigate the relationship between blood cell composition and DNA methylation age, a biomarker often used to estimate biological age. The study, involving 4,058 samples, employs a novel principal component analysis (PCA) method that addresses the collinearity of blood cell counts, providing insights into how these factors contribute to biological aging.
Background
Epigenetic clocks have gained popularity as biomarkers of biological age, yet the biological mechanisms underlying these clocks remain poorly understood. Previous findings suggested that the proportions of naïve and memory T cells could influence epigenetic aging. This study aims to clarify the role of blood cell composition in determining DNA methylation age and age acceleration.
Methods
The researchers developed a PCA method to analyze blood cell counts without the confounding effects of collinearity. They quantified the contribution of various blood cell types to DNA methylation age and age acceleration, utilizing six different epigenetic clocks. Furthermore, they examined the impact of cell composition on the relationship between age acceleration and 176 health outcomes in a larger cohort of 18,859 individuals.
Results
The findings reveal 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 between age acceleration and cell counts explains only up to 21% of the variance, with neutrophils being the primary contributors for 2nd-generation clocks. Additionally, the study validated these findings using artificial mixtures of blood cells.
Interestingly, the research indicates that blood cell composition significantly attenuates the association between age acceleration and health outcomes, although this effect is described as modest. This suggests that while DNA methylation age and age acceleration are influenced by blood cell composition, they reflect different biological processes.
Conclusions
The study concludes that DNA methylation age (DNAmAge) and age acceleration (AgeAccel) are distinct in their associations with blood cell composition. The authors emphasize that the variation in age acceleration attributed to blood cell composition has only a minor role in 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 provide evidence of clinical utility for using DNA methylation age or age acceleration as predictive biomarkers for individual health risks.
Evidence scorecard
- Analytic validity: Established
- Clinical validity: Partial
- Clinical utility: Not established
The evidence is based on primary research involving human subjects.