ArticleProceedings of the National Academy of Sciences of the United States of America2014
Metformin promotes lifespan through mitohormesis via the peroxiredoxin PRDX-2.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 187 papers, 2 of them syntheses that pooled it.
What it found
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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
187 citing papers in PubMed, 2 syntheses or guidelines pooled it, 357 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
- The effect of metformin on mortality and severity in COVID-19 patients with diabetes mellitus.Diabetes research and clinical practice · 2021 · on this mapPooled it
- Trial
- p38 MAPK and MDT-15 mediate SKN-1-dependent metformin-induced protection against mitis group streptococci in Caenorhabditis elegans.GeroScience · 2026Article
- Divergent Retrograde Signaling Pathways Coordinate Longevity and Metformin Responses in Complex I and Complex IV DeficientbioRxiv : the preprint server for biology · 2026Article
- Closing the gap in aging science: unlocking the potential of nanoparticles in senescence therapy.Biogerontology · 2026Review
- Fasting requires Peroxiredoxin 2 and Peroxiredoxin 6 to coordinate redox dependent mitochondrial and lipid remodelling in Caenorhabditis elegans.Redox biology · 2026Article
- Mitochondrial cardiomyopathy: bridging molecular mechanisms and clinical frontiers.Nature reviews. Cardiology · 2026Review
- Metformin beyond Glycemic Control: New Mechanistic Insights and Expanding Therapeutic Horizons.Diabetes & metabolism journal · 2026Review
- Translational Geroscience Strategies for Delaying Multimorbidity.ACS pharmacology & translational science · 2026Review
- Article
- Article
- Spatiotemporal dynamics of reactive oxygen species: implications for cellular homeostasis and redox therapies.Cellular & molecular biology letters · 2026Review
- Biosacetalin (1,1-Diethoxyethane) Improves Healthy Lifespan inAntioxidants (Basel, Switzerland) · 2026Article
- Therapeutic Targeting of Inflammaging and Emerging Strategies for Managing Age-Related Multimorbidity: A Narrative Review.Clinical interventions in aging · 2026Review
- Leveraging mitochondrial stress to improve healthy aging.Sports medicine and health science · 2026Review
- Mitohormesis linking metabolic dysfunction and neurodegeneration: implications for dementia and therapeutic strategies.Frontiers in molecular neuroscience · 2026Review
- Cyrene: a novel geroprotective compound that extends lifespan and healthspan in C. elegans and Drosophila.npj aging · 2025Article
- AMPK phosphorylates WIP1 to promote DNA repair and radioresistance in cancer cells.Cell death & disease · 2025Article
- Mammalian mitohormesis: from mitochondrial stressors to organismal benefits.The EMBO journal · 2025Review
127 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
9 authors at 3 institutions in 2 countries.
Funding
Abstract
The antiglycemic drug metformin, widely prescribed as first-line treatment of type II diabetes mellitus, has lifespan-extending properties. Precisely how this is achieved remains unclear. Via a quantitative proteomics approach using the model organism Caenorhabditis elegans, we gained molecular understanding of the physiological changes elicited by metformin exposure, including changes in branched-chain amino acid catabolism and cuticle maintenance. We show that metformin extends lifespan through the process of mitohormesis and propose a signaling cascade in which metformin-induced production of reactive oxygen species increases overall life expectancy. We further address an important issue in aging research, wherein so far, the key molecular link that translates the reactive oxygen species signal into a prolongevity cue remained elusive. We show that this beneficial signal of the mitohormetic pathway is propagated by the peroxiredoxin PRDX-2. Because of its evolutionary conservation, peroxiredoxin signaling might underlie a general principle of prolongevity signaling.
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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.