DNA methylation signatures reflect aging in patients with nonalcoholic steatohepatitis
| Autor: | Rohit Loomba, Nezam H. Afdhal, Robert P. Myers, Chuhan Chung, C. Stephen Djedjos, Zachary Goodman, G. Mani Subramanian, Anna Mae Diehl, Ren Xu, Yevgeniy Gindin, Stephen H. Caldwell, Michael Charlton, Eric Lawitz, Zhaoshi Jiang |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Aging Biopsy Datasets as Topic Severity of Illness Index Hepatitis Epigenesis Genetic Fibrosis Non-alcoholic Fatty Liver Disease 2.1 Biological and endogenous factors Aetiology Randomized Controlled Trials as Topic Liver Disease Aging Premature General Medicine Methylation Middle Aged CpG site Liver DNA methylation Cohort Female Collagen Research Article Adult medicine.medical_specialty Chronic Liver Disease and Cirrhosis Biology 03 medical and health sciences Clinical Trials Phase II as Topic Genetic Clinical Research Internal medicine medicine Genetics Humans Clinical Trials Epigenetics Premature Aged Hepatology Phase II as Topic Human Genome dNaM DNA Methylation medicine.disease digestive system diseases 030104 developmental biology Endocrinology Good Health and Well Being Case-Control Studies CpG Islands Digestive Diseases Biomarkers Epigenesis |
| Zdroj: | JCI insight, vol 3, iss 2 |
| ISSN: | 2379-3708 |
| Popis: | A DNA methylation (DNAm) signature (the "Horvath clock") has been proposed as a measure of human chronological and biological age. We determined peripheral blood DNAm in patients with nonalcoholic steatohepatitis (NASH) and assessed whether accelerated aging occurs in these patients. DNAm signatures were obtained in patients with biopsy-proven NASH and stage 2-3 fibrosis. The DNAm profile from one test and two validation cohorts served as controls. Age acceleration was calculated as the difference between DNAm age and the predicted age based on the linear model derived from controls. Hepatic collagen content was assessed by quantitative morphometry. The Horvath clock accurately predicts the chronological age of the entire cohort. Age acceleration was observed among NASH subjects compared with control data sets and our test controls. Age acceleration in NASH subjects did not differ by fibrosis stage but correlated with hepatic collagen content. A set of 152 differentially methylated CpG islands between NASH subjects and controls identified gene set enrichment for transcription factors and developmental pathways. Patients with NASH exhibit epigenetic age acceleration that correlates with hepatic collagen content. |
| Databáze: | OpenAIRE |
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