In the realm of biological aging, epigenetic clocks have emerged as significant biomarkers. These clocks, which estimate biological age based on DNA methylation patterns, are influenced by various factors, including blood cell composition. This study, published in Genome Medicine, investigates the relationship between blood cell types and DNA methylation age, providing insights into the biological underpinnings of these epigenetic markers.
Background
Previous research indicated that the proportions of naïve and memory T cells could affect epigenetic clocks. However, understanding the biological implications of these findings has been challenging due to the collinearity between different blood cell fractions. The authors of this study aimed to clarify these relationships by developing a principal component analysis (PCA) method that accounts for this collinearity.
Methods
The study analyzed a substantial dataset comprising 4,058 samples to quantify the contribution of blood cell composition to DNA methylation age and age acceleration, as estimated by six different epigenetic clocks. Additionally, the researchers examined the influence of cell composition on the association between age acceleration and 176 incident health outcomes using 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 role of naïve and memory T cells. In contrast, the association between age acceleration and cell counts explained up to 21% of the variance, with neutrophils being the primary contributors for 2nd-generation clocks. The study also validated these results through experiments involving artificial cell mixtures.
Interestingly, while blood cell composition significantly attenuated the association of age acceleration with various health outcomes, the overall effect was modest. This suggests that while cell composition plays a role in biological aging, it may not be the primary driver of health outcomes related to mortality and disease incidence.
Conclusions
The study concludes that DNA methylation age (DNAmAge) and age acceleration (AgeAccel) reflect different biological processes, as evidenced by their distinct associations with blood cell composition. The modest contribution of blood cell types to age acceleration’s association with health outcomes indicates that other factors may also be at play in determining biological aging and its implications for health.
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 in predicting individual health risks based on DNA methylation age.
Evidence scorecard
- Analytic validity: Established
- Clinical validity: Partial
- Clinical utility: Not established
The evidence is based on primary research findings.