Epigenetic Aging in Pediatric Crohn's Disease: A Longitudinal Analysis of DNA Methylation-Based Aging Clocks

Abstract: A recent independent study reported that patients with inflammatory bowel disease, including children with Crohn's disease, show elevated epigenetic age acceleration relative to healthy controls across several DNA methylation-based "clocks," after adjusting for blood cell-type composition and sex. It is unclear whether this finding depends on the specific software used to compute clock values, and whether the association persists over time within the same patients rather than reflecting disease activity at a single timepoint. Using the publicly available GSE112611 dataset (164 paediatric Crohn's disease patients at diagnosis, 74 non-inflammatory-bowel-disease controls, plus paired follow-up samples collected 24-36 months later), I recomputed four epigenetic clocks (Horvath, Hannum, PhenoAge, GrimAge version 2) with an independently implemented, open-source pipeline and the same adjustment strategy. PhenoAge and GrimAge version 2 age acceleration were significantly elevated in patients at diagnosis after adjustment (+6.05 years, 95% CI 3.76-8.35, p Keywords: Epigenetic clocks, DNA methylation, Paediatric Crohn's disease, Age acceleration, Longitudinal analysis. Preprint Notice: This manuscript is an open-access scientific preprint published in the Global Youth Science Journal (GYSJ) Preprints repository. It has not undergone formal journal peer review. Permanent Repository URL: https://globalyouthsciencejournal.app/preprint/202611.0018