2026-10-06T21:37:40Z https://api.figshare.com/v2/oai

oai:figshare.com:article/34024776 2026-09-29T15:35:04Z category_24184 category_24205 category_24295 item_type_5 month_year_09_2026

CellPress Symposia: Hallmarks of Aging - Sex-specific nonlinear methylation ageing trajectories Robin Grolaux (25137675) Macsue Jacques (6662246) Steve Horvath (28847) Andrew E Teschendorff (21487097) Nir Eynon (142365) Bioinformatic methods development Translational and applied bioinformatics Epigenetics (incl. genome methylation and epigenomics) Ageing Aging DNA methylation Nonlinearity Epigenetics <p dir="ltr">Aging is commonly modeled as a gradual linear decline, yet humans undergo nonlinear transitions between distinct functional states across their lifespan. 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. These findings support nonlinearity as a fundamental feature of biological aging and highlight trajectory-based approaches for identifying clinically relevant aging states.</p> 2026-09-29T15:35:04Z Image Poster 10.6084/m9.figshare.34024776.v1 https://figshare.com/articles/poster/CellPress_Symposia_Hallmarks_of_Aging_-_Sex-specific_nonlinear_methylation_ageing_trajectories/34024776 CC BY 4.0