Blood cell composition reveals distinct biological interpretation of DNA methylation age and age acceleration.

Blood cell composition accounts for up to 53% of variation in DNA methylation age, with a strong influence from naїve and memory T cell balance.

• Why it matters: Understanding the biological basis of epigenetic clocks is crucial for their use as biomarkers of aging and health, but blood cell heterogeneity complicates interpretation.
• What they did: Researchers developed a principal component analysis method to address collinearity in blood cell counts and analyzed 4,058 samples with six epigenetic clocks, also testing 18,859 individuals for health outcome associations.
• The result: They found that cell counts significantly influence DNA methylation age and age acceleration, yet only modestly affect their links to mortality and disease, indicating different underlying biological processes.