ArticleAging cell2022
Inhibition of DNA methyltransferase aberrations reinstates antioxidant aging suppressors and ameliorates renal aging.
Article in Aging cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 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
42 citing papers in PubMed, 59 citations in OpenAlex.
- Article
- Repurposing Seleno-L-Methionine as a Pleiotropic Immunomodulatory Agent to Overcome TGF-β1/HIF-Driven Immune Evasion in Clear Cell Renal Cell Carcinoma: Mechanistic Insights and Translational Therapeutic Opportunities.International journal of molecular sciences · 2026Review
- Nutritional Modulation of Epigenetic Responses to Heat Stress in Farm Animals: Evidence, Limitations and Perspectives.Animals : an open access journal from MDPI · 2026Review
- Geroprotective applications of oleuropein and hydroxytyrosol through the hallmarks of ageing.GeroScience · 2026Review
- DNA hypermethylation of FGFR2 drives fibrosis in the aging kidney.Scientific reports · 2026Article
- Review
- Glucose and Lipid Metabolic Mechanisms in Vascular Aging and Related Therapeutic Strategies.Reviews in cardiovascular medicine · 2026Review
- HIF-activated priming of TRAIL-induced cell death determines epigenetic vulnerability in kidney cancer.Cell reports. Medicine · 2026Article
- Microcystin-LR Triggers Renal Tubular Ferroptosis Through Epigenetic Repression of GPX4: Implications for Environmental Nephrotoxicity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Ferroptosis in Myocardial Fibrosis: Mechanisms and Therapeutic Insights.Antioxidants (Basel, Switzerland) · 2026Review
- The Role of DNA Methyltransferases in Urinary System Diseases.Cancer innovation · 2025Review
- Epigenetic Regulation of Aging and its Rejuvenation.MedComm · 2025Review
- Pretreatment withNutrients · 2025Article
- The Role of Klotho in Oral and Maxillofacial Diseases: Mechanisms and Research Progress.Biomolecules · 2025Review
- Hypermethylation of Klotho and Peroxisome Proliferator-Activated Receptor γ Concomitant with Overexpression of DNA Methyltransferase 1 in Adenomyosis.Reproductive sciences (Thousand Oaks, Calif.) · 2025Article
- Role of DNA methylation transferase in urinary system diseases: From basic to clinical perspectives (Review).International journal of molecular medicine · 2025Review
- DNMT aberration-incurred GPX4 suppression prompts osteoblast ferroptosis and osteoporosis.Bone research · 2024Article
- Lysosomal-Associated Protein Transmembrane 5, Tubular Senescence, and Progression of CKD.Journal of the American Society of Nephrology : JASN · 2024Article
- SAM-DNMT3A, a strategy for induction of genome-wide DNA methylation, identifies DNA methylation as a vulnerability in ER-positive breast cancers.Nature communications · 2024Article
- Enhancing antitumor activity of herceptin in HER2-positive breast cancer cells: a novel DNMT-1 inhibitor approach.Discover oncology · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA methylation alterations play mechanistic roles in aging; however, the epigenetic regulators/mediators causally involved in renal aging remain elusive. Here, we report that natural and D-galactose (D-gal)-induced aging kidneys display marked suppression of antiaging factor NRF2 (nuclear factor erythroid-derived 2-like 2) and KLOTHO, accompanied by upregulations of DNA methyltransferase (DNMT) 1/3a/3b and NRF2/KLOTHO gene promoter hypermethylations. Administration of a DNMT inhibitor SGI-1072 effectively hypomethylated the promoters, derepressed NRF2/KLOTHO, and mitigated the structural and functional alterations of renal aging in D-gal mice. Moreover, oleuropein (OLP), an olive-derived polyphenol, also displayed similar epigenetic modulation and antiaging effects. OLP inhibited the epigenetic NRF2/KLOTHO suppressions in a gain of DNMT-sensitive manner in cultured renal cells, demonstrating a strong DNA-demethylating capacity. In NRF2 knockout and KLOTHO knockdown D-gal mice, OLP exhibited reduced antiaging effects with KLOTHO displaying a prominent gene effect and effect size; consistently in KLOTHO knockdown mice, the antiaging effects of SGI-1027 were largely abrogated. Therefore, the KLOTHO recovery is critical for the antiaging effects of DNA demethylation. Collectively, our data indicate that aberrant DNMT1/3a/3b elevations and the resultant suppression of antiaging factors contribute significantly to epigenetic renal aging, which might be targeted for epigenetic intervention by synthetic or natural DNA-demethylating agents.
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.