Blood methylation framework links aging hallmarks to organ patterns across humans

In a preprint analyzing blood DNA methylation from 656 discovery and 1,394 replication human participants, researchers introduced RootMap to evaluate relationships between aging hallmarks and organ-aging patterns. The team scored 332 gene modules for intrinsic capability and defined dependencies as differences in organ-age associations based on hallmark scores. Twenty-two hallmark-organ pairs passed quality checks, with 17 of 20 retaining their direction in replication. Stem-cell maintenance linked to 12 organ modules in the discovery cohort, whereas senescence regulation was broadest in the replication cohort. Functional modules altered their scores during interventions more often than hallmark modules (25.4% versus 14.4%). Applying functional-layer filters to a protein-interaction drug screen increased candidate hit enrichment from 3.19-fold to 8.87-fold.