ArticleAging cell2022
Metformin induces S-adenosylmethionine restriction to extend the Caenorhabditis elegans healthspan through H3K4me3 modifiers.
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 27 papers, 1 of them a synthesis that pooled it.
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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
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- 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
- p38 MAPK and MDT-15 mediate SKN-1-dependent metformin-induced protection against mitis group streptococci in Caenorhabditis elegans.GeroScience · 2026Article
- Streptococcus thermophilus remodels lipid metabolism to extend healthspan in Caenorhabditis elegans through NHR-49-Delta-9 desaturase axis.GeroScience · 2026Article
- Insights into the therapeutic strategies for aging and aging-associated diseases.Signal transduction and targeted therapy · 2026Review
- LSD1-ESM1 regulates extravillous trophoblast function through metabolic reprogramming in recurrent spontaneous abortion.Journal of assisted reproduction and genetics · 2026Article
- Parental polystyrene nanoplastics exposure increases susceptibility to pathogen infection in offspring via H3K36me3-UPRCell communication and signaling : CCS · 2026Article
- Metformin Impairs Breast Cancer Growth through the Inhibition of PRMT6.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Polystyrene nanoplastics promotes inflammation and aging in young mice through the oral-gut microbiome axis.Frontiers in immunology · 2026Article
- Chelerythrine enhances anti-fungi immunity inFrontiers in immunology · 2026Article
- Jujuboside A extends healthspan and enhances resistance of oxidative stress inFrontiers in pharmacology · 2026Article
- Hypoxia inducible factor 1 subunit alpha mediates autophagy disorder of oral lichen planus by regulating lysosomal pathway.Frontiers in immunology · 2026Article
- Parental sodium benzoate diet induces fat accumulation in offspring via histone H3K9me3 and SKN-1/Nrf2.Current research in food science · 2026Article
- Methionine restriction alleviates kidney fibrosis through epigenetic repression of the TGF-β-Smad3-Hoxc8/P-TEFb axis.Nature communications · 2025Article
- Ginkgolide a enhances the resistance to pathogen infection through mitochondrial unfolded protein response.Cellular and molecular life sciences : CMLS · 2025Article
- Metformin and insulin exacerbate one-carbon metabolism deficits in pregnant growth restricted rats and impacts the placenta, fetal liver and pancreas.The Journal of physiology · 2025Article
- Parental S-adenosylmethionine diet defines offspring immune response via histone H3K4me3 complex and Endoplasmic Reticulum UPR.Cell communication and signaling : CCS · 2025Article
- Epigenetic Regulation of Aging and its Rejuvenation.MedComm · 2025Review
- Article
- Enterococcus faecalis SI-FC-01 enhances the stress resistance and healthspan of C. elegans via AKT signaling pathway.Scientific reports · 2025Article
- Mechanisms and rationales of SAM homeostasis.Trends in biochemical sciences · 2025Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metformin, a widely prescribed first-line drug for the treatment of type II diabetes mellitus, has been shown to extend lifespan and delay the onset of age-related diseases. The precisely mechanisms by which these effects are realized remain elusive. We find that metformin exposure is restricted to adults, which is sufficient to extend lifespan. However, limiting metformin exposure to the larvae has no significant effect on Caenorhabditis elegans longevity. Here, we show that after metformin treatment, the level of S-adenosylmethionine (SAM) is reduced in adults but not in the larvae. Potential mechanisms by which reduced SAM might increase lifespan include altering the histone methylation. However, the molecular connections between metformin, SAM limitation, methyltransferases, and healthspan-associated phenotypes are unclear. Through genetic screening of C. elegans, we find that metformin promotes the healthspan through an H3K4 methyltransferase/demethylase complex to downregulate the targets, including mTOR and S6 kinase. Thus, our studies provide molecular links between meformin, SAM limitation, histone methylation, and healthspan and elucidate the mode action of metformin-regulated healthspan extension will boost its therapeutic application in the treatment of human aging and age-related diseases.
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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.