Sex-specific nonlinear DNA methylation aging trajectories reveal biomarkers of cancer risk and inflammation.

ABSTRACT:

Background

Aging is a multi-modal process, leaving distinct molecular signatures across the epigenome. DNA methylation is among the most robust biomarkers of biological aging, yet most studies assume linear age relationships and analyze mixed-sex cohorts, overlooking known sex differences. Such approaches risk obscuring critical nonlinear transitions and sex-specific trajectories.

Results

We develop SNITCH, a computational framework to detect complex nonlinear methylation trajectories and disentangle shared from sex-divergent patterns. Applied to the array-derived whole-blood methylomes from 252 females and 246 males (ages 19-90 years), SNITCH reveals convergent and divergent epigenetic aging pathways independent of immune cell composition. Nonlinear trajectories are enriche

SUBMITTER: Grolaux R 

PROVIDER: S-EPMC12870970 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature