Epigenetic clocks have emerged as widely used biomarkers for assessing biological age, yet the biological mechanisms underlying these clocks remain poorly understood. This study investigates the role of blood cell composition in influencing DNA methylation age and age acceleration, providing insights into their biological interpretations.
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 imply that changes in cell composition can predict health outcomes.
Evidence scorecard
- Analytic validity: Established
- Clinical validity: Partial
- Clinical utility: Not established
The evidence is derived from a primary research study involving human participants.
The study utilized a principal component analysis (PCA) method that is robust against collinearity among blood cell counts. This approach allowed the researchers to quantify the contribution of various blood cell types to DNA methylation age and age acceleration, using a dataset of 4,058 samples.
Findings indicated that up to 53% of the variation in DNA methylation age could be attributed to blood cell counts, particularly highlighting the influence of naïve and memory T cells. In contrast, the association between age acceleration and cell counts explained only up to 21% of the variance, with neutrophils playing a significant role in 2nd-generation epigenetic clocks.
Moreover, the study examined the impact of blood cell composition on the relationship between age acceleration and 176 incident health outcomes across a larger cohort of 18,859 individuals. While the results suggested that cell composition could attenuate the association between age acceleration and health outcomes, the effect was described as modest.
In conclusion, the study emphasizes that DNA methylation age and age acceleration reflect different biological processes, influenced by blood cell composition. However, the contribution of blood cell composition to the association with mortality and disease outcomes appears to be limited.