Probing epigenetic clocks as a rational markers of biological age using blood cell counts
Jonkman, T. H.; van Zwet, E. W.; Heijmans, B. T.
Show abstract
BackgroundEpigenetic clocks are widely applied biomarkers of biological age, but their biological underpinnings remain unclear. We previously showed that epigenetic clocks are affected by naive and memory T cell proportions, suggesting blood cell composition as a potential driver. MethodsHere, we quantify the contribution of cell counts to DNA methylation age (DNAmAge) and age acceleration (AgeAccel) estimated by six 1st- or 2nd-generation epigenetic clocks. First, we present a principal component analysis (PCA) method that is robust to collinearity of blood cell counts and show this provides biologically meaningful insights. ResultsApplying this approach, we find strong associations between DNAmAge and cell counts, particularly with naive and memory T cells. In contrast, associations between AgeAccel and cell counts are weaker and, particularly for 2nd-generation clocks, primarily involve neutrophils. We validate these findings in an external dataset of artificial cell mixtures. ConclusionsWe conclude that DNAmAge and AgeAccel reflect different biological processes.
Matching journals
The top 3 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- A novel framework to build saliva-based DNA methylation biomarkers: quantifying systemic chronic inflammation as a case study 95%
- Epigenetic clock and methylation study of oocytes from a bovine model of reproductive aging 95%
- Body weight at young adulthood and association with epigenetic aging and lifespan in the BXD murine family 95%
Similar papers in this journal
- A computational solution for bolstering reliability of epigenetic clocks: Implications for clinical trials and longitudinal tracking 96%
- Multi-omic profiling of primary mouse neutrophils reveals a pattern of sex and age-related functional regulation 96%
- A Novel Blood-Based Epigenetic Clock for Intrinsic Capacity Predicts Mortality and is Associated with Clinical, Immunological and Lifestyle Factors 95%
Similar papers in this journal
- DNA methylation clocks struggle to distinguish inflammaging from healthy aging, but feature rectification improves coherence and enhances detection of inflammaging 96%
- Epigenetic clock and methylation studies in the rhesus macaque 96%
- Development of a novel aging clock based on chromatin accessibility 95%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.