DNA methylation age and age acceleration are important biomarkers used to estimate biological age. However, the biological mechanisms underlying these epigenetic clocks have not been fully understood. This study investigates the role of blood cell composition in influencing DNA methylation age and age acceleration.
What this study does not show
This research does not establish a direct causal relationship between blood cell composition and health outcomes, nor does it provide definitive insights into the clinical utility of DNA methylation age in predicting health risks.
Evidence scorecard
- Analytic validity: Established
- Clinical validity: Partial
- Clinical utility: Not established
The study employs a robust principal component analysis (PCA) method to address the collinearity of blood cell counts, allowing for a clearer understanding of how these factors contribute to DNA methylation age. The analysis includes 4,058 samples and examines the influence of cell composition on the association between age acceleration and 176 incident health outcomes from a larger cohort of 18,859 individuals.
Findings indicate 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 a maximum of 21% of the variance, primarily involving neutrophils for 2nd-generation clocks.
Interestingly, while cell composition does attenuate the association of age acceleration with health outcomes, the effect is modest. This suggests that DNA methylation age and age acceleration reflect different biological processes, with implications for understanding aging and health.
Overall, this study highlights the complexity of biological aging and the need for further research to clarify the role of blood cell composition in health outcomes.