ArticleFrontiers in cell and developmental biology2020
Effect of Metformin on Cardiac Metabolism and Longevity in Aged Female Mice.
Article in Frontiers in cell and developmental biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 4 of them syntheses that pooled it.
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
22 citing papers in PubMed, 4 syntheses or guidelines pooled it, 28 citations in OpenAlex.
- Rapamycin, Not Metformin, Mirrors Dietary Restriction-Driven Lifespan Extension in Vertebrates: A Meta-Analysis.Aging cell · 2025Pooled it
- Repurposing effect of cardiovascular-metabolic drug to increase lifespan: a systematic review of animal studies and current clinical trial progress.Frontiers in pharmacology · 2024Pooled it
- Sex differences in pharmacological interventions and their effects on lifespan and healthspan outcomes: a systematic review.Frontiers in aging · 2023Pooled it
- Pooled it
- Oxidative stress and inflammation in neurodegenerative disorders.Archives of toxicology · 2026Review
- Hormones, heat, and health: a comprehensive review of sex-based differences in brown and beige fat biology.Biology of sex differences · 2025Review
- Sex-specific response to A1BG loss results in female dilated cardiomyopathy.Biology of sex differences · 2025Article
- Integrating Machine Learning with Multi-Omics Technologies in Geroscience: Towards Personalized Medicine.Journal of personalized medicine · 2024Review
- Data-dependent and -independent acquisition lipidomics analysis reveals the tissue-dependent effect of metformin on lipid metabolism.Metabolomics : Official journal of the Metabolomic Society · 2024Article
- Effects of Metformin on Ischemia/Reperfusion Injury: New Evidence and Mechanisms.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Rilmenidine extends lifespan and healthspan in Caenorhabditis elegans via a nischarin I1-imidazoline receptor.Aging cell · 2023Article
- Targeting Mitochondria to Control Ageing and Senescence.Pharmaceutics · 2023Review
- Cardiovascular aging: from cellular and molecular changes to therapeutic interventions.The journal of cardiovascular aging · 2023Article
- Epigenetic regulation of aging: implications for interventions of aging and diseases.Signal transduction and targeted therapy · 2022Review
- Metformin Prevents Endothelial Dysfunction in Endometriosis through Downregulation of ET-1 and Upregulation of eNOS.Biomedicines · 2022Article
- Peroxisome proliferator-activated receptor γ coactivator 1α maintains NADLife medicine · 2022Article
- SIRT6 in Vascular Diseases, from Bench to Bedside.Aging and disease · 2022Article
- Common Pathogenetic Mechanisms Underlying Aging and Tumor and Means of Interventions.Aging and disease · 2022Article
- Metformin: Sex/Gender Differences in Its Uses and Effects-Narrative Review.Medicina (Kaunas, Lithuania) · 2022Review
- Metformin Treatment in Old Rats and Effects on Mitochondrial Integrity.Rejuvenation research · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The antidiabetic drug metformin exerts pleiotropic effects on multiple organs, including the cardiovascular system. Evidence has shown that metformin improves healthspan and lifespan in male mice, yet its lifespan lengthening effect in females remains elusive. We herein demonstrated that metformin fails to extend the lifespan in female mice. Compared to 2-month-old young controls, 20-month-old female mice showed a spectrum of degenerative cardiac phenotypes alongside significant alterations in the extracellular matrix composition. Despite lowered reactive oxygen species production, long-term metformin treatment did not improve cardiac function in the aged female mice. In contrast, RNA sequencing analyses demonstrated that metformin treatment elevated the extracellular matrix-related gene while lowering oxidative phosphorylation-related gene expression in the heart. In addition, metformin treatment induced metabolic reprogramming that suppressed mitochondrial respiration but activated glycolysis (i.e., Warburg effect) in cultured primary cardiomyocytes and macrophages, thereby sustaining an inflammatory status and lowering ATP production. These findings suggest the unexpected detrimental effects of metformin on the regulation of cardiac homeostasis and longevity in female mice, reinforcing the significance of comprehensive testing prior to the translation of metformin-based novel therapies.
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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.