Telomere attrition marks disease severity in chronic cholestatic liver diseases
Epigenetic telomere length analysis in patients with sclerosing or biliary cholangitis reveals converging markers of accelerated biological aging.
In a human observational study, researchers evaluated DNA methylation-derived telomere length in 474 patients with primary sclerosing cholangitis, 291 patients with primary biliary cholangitis, and matched controls. The team investigated associations between this marker of cellular turnover, clinical outcomes, the PREsTO risk score, and epigenetic age acceleration measured by AgeAccelGrim. Patients with primary sclerosing cholangitis had significantly shorter age-adjusted telomere lengths than controls. Across the cohorts, shortened telomere length independently correlated with disease severity in primary sclerosing cholangitis. Together with epigenetic age acceleration, these converging biological aging signatures support a model of accelerated biological aging in chronic cholestatic liver diseases.
Why it matters
The findings suggest that cellular turnover and biological aging signatures converge during chronic organ pathology. Understanding these aging metrics could provide insight into progressive biliary injury and fibrosis.
Caveats
The study uses an observational design, which cannot establish whether accelerated biological aging drives disease progression. The results are also limited to cohorts with these two specific chronic cholestatic conditions.
- Epigenetic alterations
- Telomere attrition
- Cholestatic liver disease
- Fibrosis
- Primary biliary cholangitis
- Primary sclerosing cholangitis
- DNAmTL
- GrimAge
- PREsTO score
- Homo sapiens
The paper
Accelerated Biological Aging in Cholestatic Liver Disease: Telomere Attrition and Association With Disease Severity
Alsakarneh SG, Juran BD, Fernandez J et al.
Alimentary Pharmacology & Therapeutics · 29 Sep 2026