ArticleAging cell2016
Metformin-mediated increase in DICER1 regulates microRNA expression and cellular senescence.
Article in Aging cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers.
What it found
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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.
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Who cites it
117 citing papers in PubMed, 198 citations in OpenAlex.
- MicroRNAs Associated with Metformin Treatment in the Diabetes Prevention Program.International journal of molecular sciences · 2024Trial
- Metformin as an Innate Immune Modulator: Metabolic and Epigenetic Reprogramming of Innate Immune Cells and Therapeutic Implications.Current issues in molecular biology · 2026Review
- Energy stress activates AMPK to arrest mitochondria via phosphorylation of TRAK1.The Journal of cell biology · 2026Article
- SIRT1 Activators as Geroprotective Agents in Brain Aging: Mechanisms and Therapeutic Potential.Neuromolecular medicine · 2026Review
- Aging-associated mitochondrial circular RNAs.Aging · 2026Article
- Natural Products as Anti-Senescence-Associated Secretory Phenotype (SASP) Agents.Current medicinal chemistry · 2026Review
- Cardiometabolic Therapies Shape Non-Coding RNA Landscapes in Cardiovascular Fibrosis.Metabolites · 2025Review
- The dynamics of DNA methylation, histone methylation and acetylation during oocyte aging in mammalian species and possible interventions to regulate them.Journal of assisted reproduction and genetics · 2025Review
- Biomarkers of Cellular Senescence in Type 2 Diabetes Mellitus.Aging cell · 2025Article
- Article
- 3D models to study therapy-induced senescence: where do we stand now?Cytotechnology · 2025Review
- The Anti-Aging Mechanism of Metformin: From Molecular Insights to Clinical Applications.Molecules (Basel, Switzerland) · 2025Review
- Ovarian Aging: The Silent Catalyst of Age-Related Disorders in Female Body.Aging and disease · 2025Review
- DICER1: The Argonaute Endonuclease Family Member and Its Role in Pediatric and Youth Pathology.Biology · 2025Review
- Mitochondrial dysfunction and alveolar type II epithelial cell senescence: The destroyer and rescuer of idiopathic pulmonary fibrosis.Frontiers in cell and developmental biology · 2025Review
- Co-Delivery of Valsartan and Metformin from a Thermosensitive Hydrogel-Nanoparticle System Promotes Collagen Production in Proliferating and Senescent Primary Human Dermal Fibroblasts.Biomacromolecules · 2024Article
- To target cellular senescence in diabetic kidney disease: the known and the unknown.Clinical science (London, England : 1979) · 2024Review
- Exploring the Interplay between Cellular Senescence, Immunity, and Fibrosing Interstitial Lung Diseases: Challenges and Opportunities.International journal of molecular sciences · 2024Review
- New Molecules in Type 2 Diabetes: Advancements, Challenges and Future Directions.International journal of molecular sciences · 2024Review
- Review
57 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Metformin, an oral hypoglycemic agent, has been used for decades to treat type 2 diabetes mellitus. Recent studies indicate that mice treated with metformin live longer and have fewer manifestations of age-related chronic disease. However, the molecular mechanisms underlying this phenotype are unknown. Here, we show that metformin treatment increases the levels of the microRNA-processing protein DICER1 in mice and in humans with diabetes mellitus. Our results indicate that metformin upregulates DICER1 through a post-transcriptional mechanism involving the RNA-binding protein AUF1. Treatment with metformin altered the subcellular localization of AUF1, disrupting its interaction with DICER1 mRNA and rendering DICER1 mRNA stable, allowing DICER1 to accumulate. Consistent with the role of DICER1 in the biogenesis of microRNAs, we found differential patterns of microRNA expression in mice treated with metformin or caloric restriction, two proven life-extending interventions. Interestingly, several microRNAs previously associated with senescence and aging, including miR-20a, miR-34a, miR-130a, miR-106b, miR-125, and let-7c, were found elevated. In agreement with these findings, treatment with metformin decreased cellular senescence in several senescence models in a DICER1-dependent manner. Metformin lowered p16 and p21 protein levels and the abundance of inflammatory cytokines and oncogenes that are hallmarks of the senescence-associated secretory phenotype (SASP). These data lead us to hypothesize that changes in DICER1 levels may be important for organismal aging and to propose that interventions that upregulate DICER1 expression (e.g., metformin) may offer new pharmacotherapeutic approaches for age-related disease.
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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.