Epigenetic clocks have emerged as significant biomarkers for assessing biological age, yet their biological foundations remain poorly understood. In this study published in Genome Medicine, researchers investigated the role of blood cell composition in influencing DNA methylation age and age acceleration.
Background
Previous studies have suggested that variations in epigenetic clocks could be influenced by the proportions of different T cell types in the blood. This research aims to clarify these associations by developing a robust principal component analysis (PCA) method that accounts for the collinearity often present in blood cell count data.
Methods
The study analyzed a total of 4,058 samples to quantify how much cell composition contributes to DNA methylation age and age acceleration, as estimated by six different epigenetic clocks. Furthermore, the researchers examined the relationship between age acceleration and 176 incident health outcomes in a larger cohort of 18,859 individuals.
Results
The findings revealed that up to 53% of the variation in DNA methylation age could be attributed to blood cell counts, particularly highlighting the balance between naïve and memory T cells. In contrast, the associations between age acceleration and blood cell counts explained a weaker variance of up to 21%, with neutrophils playing a significant role in 2nd-generation clocks.
Interestingly, the study also found that blood cell composition significantly attenuated the association of age acceleration with various health outcomes, although this effect was modest. This suggests that while cell composition impacts biological age assessments, its contribution to health outcomes may be limited.
Conclusions
The research indicates that DNA methylation age (DNAmAge) and age acceleration (AgeAccel) reflect different biological processes, influenced by blood cell composition. The study underscores the complexity of biological aging and the need for further exploration into how these factors interact with health outcomes.
What this study does not show
This study does not establish a direct causal relationship between blood cell composition and specific health outcomes, nor does it provide definitive conclusions regarding the clinical utility of epigenetic clocks in predicting health risks.
Evidence scorecard
- Analytic validity: Established
- Clinical validity: Partial
- Clinical utility: Not established
The evidence is based on primary research involving human samples.