Epigenetic clocks, which are biomarkers of biological age, have gained attention for their potential to reflect an individual’s health status and longevity. However, the underlying biological mechanisms that drive these clocks remain poorly understood. In a recent study published in Genome Medicine, researchers investigated the role of blood cell composition in influencing DNA methylation age and age acceleration.
What this study does not show
While the study identifies associations between blood cell composition and DNA methylation metrics, it does not establish causation or provide direct implications for clinical practice.
The researchers developed a principal component analysis (PCA) method that accounts for the collinearity of blood cell counts, allowing them to derive biologically meaningful insights. They analyzed data from 4,058 samples to quantify the contribution of various blood cell types to DNA methylation age and age acceleration, as estimated by six different epigenetic clocks.
One of the key findings was that up to 53% of the variation in DNA methylation age could be attributed to blood cell counts, particularly the balance between naïve and memory T cells. In contrast, the association between age acceleration and blood cell counts explained a maximum of 21% of the variance, with neutrophils playing a significant role in 2nd-generation clocks.
Furthermore, the study examined the influence of cell composition on the relationship between age acceleration and 176 incident health outcomes in a larger cohort of 18,859 individuals. The results indicated that while cell composition significantly attenuated the association between age acceleration and health outcomes, this effect was modest.
In conclusion, the study highlights that DNA methylation age and age acceleration are influenced by different aspects of blood cell composition, suggesting they reflect distinct biological processes. However, the contribution of blood cell composition to age acceleration’s association with mortality and disease outcomes appears to be minor.
Evidence scorecard
- Analytic validity: Established
- Clinical validity: Partial
- Clinical utility: Not established
The evidence is based on primary research involving human subjects.