ArticleGeroScience2020
DNA methylation and histone acetylation changes to cytochrome P450 2E1 regulation in normal aging and impact on rates of drug metabolism in the liver.
Article in GeroScience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 42 citations in OpenAlex.
- Effect of Perioperative Dexmedetomidine Anesthesia on Prognosis of Elderly Patients with Gastrointestinal Tumor Surgery.Computational and mathematical methods in medicine · 2022Trial
- CYP2E1 and CYP2D6 in Anti-Tuberculosis Drug-Induced Liver Injury: Mechanisms, Epigenetic Regulation, and Translational Implications.Clinical and translational science · 2026Review
- Epigenetic modifications in cancer drug resistance: molecular mechanisms and therapeutic interventions.Molecular biomedicine · 2026Review
- DNA methylation of antiseizure medication metabolism genes and pharmacokinetic changes in adult epilepsy patients treated with the modified Atkins diet.Genes & nutrition · 2026Article
- The Pivotal Role of GR-CAR Pathway in Fetal Programming of Hepatic Cytochrome P450 3A Alteration in Adulthood.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Protective effect of exercise on metabolic dysfunction‑associated fatty liver disease: Potential epigenetic mechanisms (Review).International journal of molecular medicine · 2025Review
- Article
- Genome-wide analysis of hepatic DNA methylation reveals impact of epigenetic aging on xenobiotic metabolism and transport genes in an aged mouse model.GeroScience · 2024Article
- The Future of Pharmacogenomics: Integrating Epigenetics, Nutrigenomics, and Beyond.Journal of personalized medicine · 2024Review
- Epigenetic regulation of drug metabolism in aging: utilizing epigenetics to optimize geriatric pharmacotherapy.Pharmacogenomics · 2024Review
- Antioxidant System and Endoplasmic Reticulum Stress in Cataracts.Cellular and molecular neurobiology · 2023Review
- DNA Methylation in Alcohol Use Disorder.International journal of molecular sciences · 2023Review
- Epigenetic Mechanisms Contribute to Intraindividual Variations of Drug Metabolism Mediated by Cytochrome P450 Enzymes.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- The Aryl Hydrocarbon Receptor, Epigenetics and the Aging Process.The journal of nutrition, health & aging · 2023Article
- The Roles of Myeloid Cells in Aging-related Liver Diseases.International journal of biological sciences · 2023Review
- Effects of ABCB1 DNA methylation in donors on tacrolimus blood concentrations in recipients following liver transplantation.British journal of clinical pharmacology · 2022Article
- Epigenetics in drug disposition & drug therapy: symposium report of the 24Drug metabolism reviews · 2022Review
- GSDMs are potential therapeutic targets and prognostic biomarkers in clear cell renal cell carcinoma.Aging · 2022Article
- Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Aging is associated with reduced liver function that may increase the risk for adverse drug reactions in older adults. We hypothesized that age-related changes to epigenetic regulation of genes involved in drug metabolism may contribute to this effect. We reviewed published epigenome-wide studies of human blood and identified the cytochrome P450 2E1 (CYP2E1) gene as a top locus exhibiting epigenetic changes with age. To investigate potential functional changes with age in the liver, the primary organ of drug metabolism, we obtained liver tissue from mice aged 4-32 months from the National Institute on Aging. We assayed global DNA methylation (5-methylcytosine, 5mC), hydroxymethylation (5-hydroxymethylcytosine, 5hmC), and locus-specific 5mC and histone acetylation changes around mouse Cyp2e1. The mouse livers exhibit significant global decreases in 5mC and 5hmC with age. Furthermore, 5mC significantly increased with age at two regulatory regions of Cyp2e1 in tandem with decreases in its gene and protein expressions. H3K9ac levels also changed with age at both regulatory regions of Cyp2e1 investigated, while H3K27ac did not. To test if these epigenetic changes are associated with varying rates of drug metabolism, we assayed clearance of the CYP2E1-specific probe drug chlorzoxazone in microsome extracts from the same livers. CYP2E1 intrinsic clearance is associated with DNA methylation and H3K9ac levels at the Cyp2e1 locus but not with chronological age. This suggests that age-related epigenetic changes may influence rates of hepatic drug metabolism. In the future, epigenetic biomarkers could prove useful to guide dosing regimens in older adults.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.