ArticleAging cell2022
ZMAT3 hypomethylation contributes to early senescence of preadipocytes from healthy first-degree relatives of type 2 diabetics.
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 21 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
21 citing papers in PubMed, 36 citations in OpenAlex.
- ZMAT3 alleviates cell death in Fanconi anemia via adaptation of sphingolipid metabolism.Science advances · 2026Article
- Progranulin deficiency induces premature vascular senescence and dysfunction.American journal of physiology. Heart and circulatory physiology · 2026Article
- Carrier free oral Co-delivery of atorvastatin via baicalein-copper-network for atherosclerosis therapy through senescence reversal and multi-mechanistic synergy.Bioactive materials · 2026Article
- ORANGE: a machine learning approach for modeling tissue-specific aging from transcriptomic data.Briefings in bioinformatics · 2026Article
- Senotherapeutics for metabolic disease and diabetic complications.Journal of internal medicine · 2026Review
- Physical training reduces cell senescence and associated insulin resistance in skeletal muscle.Molecular metabolism · 2025Article
- White adipose tissue in type 2 diabetes and the effect of antidiabetic drugs.Diabetology & metabolic syndrome · 2025Review
- Interplay between epigenetics, senescence and cellular redox metabolism in cancer and its therapeutic implications.Redox biology · 2024Review
- The potential for senotherapy as a novel approach to extend life quality in veterinary medicine.Frontiers in veterinary science · 2024Review
- Altered H3K4me3 profile at the TFAM promoter causes mitochondrial alterations in preadipocytes from first-degree relatives of type 2 diabetics.Clinical epigenetics · 2023Article
- The impact of cellular senescence in human adipose tissue.Journal of cell communication and signaling · 2023Review
- PBMC MicroRNAs: Promising Biomarkers for the Differential Diagnosis of COVID-19 Patients with Abnormal Coagulation Indices.Current microbiology · 2023Article
- Increased cell senescence in human metabolic disorders.The Journal of clinical investigation · 2023Review
- Short-term physical exercise controls age-related hyperinsulinemia and improves hepatic metabolism in aged rodents.Journal of endocrinological investigation · 2023Article
- Review
- Investigation of the shared molecular mechanisms and hub genes between myocardial infarction and depression.Frontiers in cardiovascular medicine · 2023Article
- Epigenetic regulation of aging: implications for interventions of aging and diseases.Signal transduction and targeted therapy · 2022Review
- Cellular senescence and senolytics: the path to the clinic.Nature medicine · 2022Review
- Epigenetic Reprogramming of the Inflammatory Response in Obesity and Type 2 Diabetes.Biomolecules · 2022Review
- Glyoxalase 1 knockdown induces age-related β-cell dysfunction and glucose intolerance in mice.EMBO reports · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Senescence of adipose precursor cells (APC) impairs adipogenesis, contributes to the age-related subcutaneous adipose tissue (SAT) dysfunction, and increases risk of type 2 diabetes (T2D). First-degree relatives of T2D individuals (FDR) feature restricted adipogenesis, reflecting the detrimental effects of APC senescence earlier in life and rendering FDR more vulnerable to T2D. Epigenetics may contribute to these abnormalities but the underlying mechanisms remain unclear. In previous methylome comparison in APC from FDR and individuals with no diabetes familiarity (CTRL), ZMAT3 emerged as one of the top-ranked senescence-related genes featuring hypomethylation in FDR and associated with T2D risk. Here, we investigated whether and how DNA methylation changes at ZMAT3 promote early APC senescence. APC from FDR individuals revealed increases in multiple senescence markers compared to CTRL. Senescence in these cells was accompanied by ZMAT3 hypomethylation, which caused ZMAT3 upregulation. Demethylation at this gene in CTRL APC led to increased ZMAT3 expression and premature senescence, which were reverted by ZMAT3 siRNA. Furthermore, ZMAT3 overexpression in APC determined senescence and activation of the p53/p21 pathway, as observed in FDR APC. Adipogenesis was also inhibited in ZMAT3-overexpressing APC. In FDR APC, rescue of ZMAT3 methylation through senolytic exposure simultaneously downregulated ZMAT3 expression and improved adipogenesis. Interestingly, in human SAT, aging and T2D were associated with significantly increased expression of both ZMAT3 and the P53 senescence marker. Thus, DNA hypomethylation causes ZMAT3 upregulation in FDR APC accompanied by acquisition of the senescence phenotype and impaired adipogenesis, which may contribute to FDR predisposition for T2D.
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.