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

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<0.00001; +5.77 years, 95% CI 4.41-7.12, p<0.00001), consistent with the original report and stable when chronological age was added as a sensitivity covariate. In the previously unanalysed follow-up samples, age acceleration decreased significantly within the same patients for Hannum, PhenoAge, and GrimAge version 2 (all p<0.00001), and the adjusted association with controls was no longer detectable at follow-up for any clock (all p>0.10). These results replicate the cross-sectional association under a different pipeline and show that age-acceleration measures decreased within this cohort over 24-36 months; regression to the mean is an alternative explanation for that decrease I cannot rule out with this design.