Blood cell composition explains substantial variation in DNA methylation age
Cell counts explain less variation in age acceleration and only modestly affect its links to mortality and 176 incident health outcomes.
Genome medicine · Jonkman TH et al. · Paper published 2 Oct 2026
In a human study analyzing 4,058 samples, researchers evaluated how blood cell composition influences DNA methylation age and age acceleration across six first- and second-generation epigenetic clocks. Using a collinearity-robust principal component analysis method, the team found that cell counts accounted for up to 53% of the variation in DNA methylation age, driven strongly by the ratio between naive and memory T cells. In contrast, cell composition explained up to 21% of the variation in age acceleration, with second-generation clocks primarily tied to neutrophil levels. The team validated these patterns using artificial cell mixtures. Across a separate dataset of 18,859 individuals, cell composition caused only modest attenuation in the associations between age acceleration and 176 incident health outcomes, indicating that cell shifts contribute minimally to these disease associations.
Why it matters
The findings show that DNA methylation age and age acceleration reflect distinct biological processes. They clarify that immune cell shifts primarily influence raw epigenetic age estimates rather than disease-predictive age acceleration.
Caveats
The findings rely on observational human data, and the attenuation of disease risk associations by cell composition remained modest.
Written from the paper’s abstract, and every claim checked against it before publishing. Read the paper for the full methods and data.
The paper
Blood cell composition reveals distinct biological interpretation of DNA methylation age and age acceleration
Jonkman TH, Richmond A, BIOS Consortium et al.
Genome medicine · 2 Oct 2026 · Peer-reviewed
- Relevance
- Core geroscience
- News value
- Important
- Evidence
- Humans
- Status
- Peer-reviewed
More on Aging clocks
See allBiological age uncertainty independently predicts mortality and health decline in humans
Researchers derived biological age uncertainty across UK Biobank participants, finding that higher uncertainty reflects reduced physiological coherence and predicts worse health outcomes.
medRxiv · Li Y et al.
Organ age acceleration and mortality risk reflect distinct biological processes
Multi-omics clocks across fourteen organs reveal divergent molecular programs and uncover thirteen candidate genes separating age acceleration from mortality.
Research Square · Na R et al.
Retinal imaging model predicts age and reveals sex differences in human aging
The retinal age gap correlates with mortality, disease risks, and sex-specific genetic pathways in more than 71,000 UK Biobank participants.
Nature communications · Trofimova O et al.
Kidney tubular epithelial cells drive accelerated epigenetic aging in disease
A cross-species single-cell atlas links injured human kidney cells and aged mouse kidneys to shared chromatin reorganization and impaired repair.
Nature aging · Jeong H et al.
Chronological age prediction does not prove biological age measurement
Researchers show that standard age-trained clocks reflect task-specific statistics rather than true biological aging constructs, limiting how researchers interpret clock gaps and rejuvenation.
bioRxiv · Song S et al.