CellPress Symposia: Hallmarks of Aging - Sex-specific nonlinear methylation ageing trajectories

Identifying these transition dynamics is critical, as intervention windows may emerge only before periods of accelerated molecular change. Here, we present a framework for studying aging as a nonlinear process using DNA methylation dynamics as a proof of concept.

We developed a computational approach that detects complex nonlinear methylation trajectories while distinguishing shared and sex-specific aging patterns. Applied to whole-blood methylomes from individuals aged 19-90 years, we identified coordinated nonlinear trajectories independent of immune cell composition, enriched for developmental and oncogenic transcription factor binding sites, including NF1 and REST. Importantly, a female-specific nonlinear trajectory was prospectively associated with cancer onset and systemic inflammation in an independent cohort.