Study Decodes What Epigenetic Clocks Measure and Adds New Transcriptomic Scores

Linking DNA methylation with gene expression gives a clearer, pathway-specific view of five aging clocks that improves prediction of disease and death.

Overview

The USC Leonard Davis–led analysis, publicized on Friday, compared five widely used epigenetic clocks in 3,227 blood samples from the U.S. Health and Retirement Study and found each clock reflects different biological pathways.
Researchers mapped DNA methylation signals to gene-expression programs and showed clocks emphasize distinct processes such as energy balance, cell growth, immune activation, and inflammatory signaling.
The team created transcriptomic aging gene scores (TAGS) based on gene-expression data and showed that TAGS alone or combined with methylation often predicted frailty, walking speed, several chronic diseases, and mortality better than methylation-only clocks.
Authors say the pathway-level map makes the clocks less of a black box and gives researchers a way to choose biomarkers that match specific study goals, for example immune-focused versus metabolism-focused work.
Broader validation in other cohorts and clinical settings is the next step, and the work could change how aging biomarkers are used in research, clinical trials, and risk stratification for older adults.