Activation of AMPK by the putative dietary restriction mimetic metformin is insufficient to extend lifespan in Drosophila
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The biguanide drug, metformin, commonly used to treat type-2 diabetes, has been shown to extend lifespan and reduce fecundity in C. elegans through a dietary restriction-like mechanism via the AMP-activated protein kinase (AMPK) and the AMPK-activating kinase, LKB1. We have investigated whether the longevity-promoting effects of metformin are evolutionarily conserved using the fruit fly, Drosophila melanogaster. We show here that while feeding metformin to adult Drosophila resulted in a robust activation of AMPK and reduced lipid stores, it did not increase lifespan in either male or female flies. In fact, we found that when administered at high concentrations, metformin is toxic to flies. Furthermore, no decreases in female fecundity were observed except at the most toxic dose. Analysis of intestinal physiology after metformin treatment suggests that these deleterious effects may result from disruptions to intestinal fluid homeostasis. Thus, metformin appears to have evolutionarily conserved effects on metabolism but not on fecundity or lifespan.
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Metformin does not extend longevity in Drosophila.
“(although not in Drosophila(275))”
From Metformin, the Aspirin of the 21st Century: Its Role in Gestational Diabetes Mellitus, Prevention of Preeclampsia and Cancer, and the Promotion of Longevity (2017) · cites this paper as [275]
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- Authors
- Slack, C., Foley, A., & Partridge, L.
- Affiliations
- University College London (GB)
- Max Planck Institute for Biology of Ageing (DE)
- Corresponding author
- Slack, Cathy
- Foley, Andrea
- Partridge, Linda
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2012-10-16
- Volume
- 7
- Issue
- 10
- Pages
- e47699
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3473082
- OpenAlex
- W2101468528
- Cited by
- 199
- References
- 52
- Citations by year
- 2026: 10 · 2025: 7 · 2024: 14 · 2023: 15 · 2022: 14 · 2021: 10 · 2020: 21 · 2019: 19 · 2018: 12 · 2017: 16 · 2016: 18 · 2015: 13 · 2014: 12 · 2013: 18
- FWCI
- 4.46
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Aston Publications Explorer (Aston University) (acceptedVersion)
- Warwick Research Archive Portal (University of Warwick) (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- UCL Discovery (University College London) (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Wellcome Trust
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Keywords
- metformin, AMPK, lifespan extension, Drosophila melanogaster, LKB1, fecundity, lipid stores, drug toxicity, biguanides
- MeSH terms
- Animals, Diet, Drosophila melanogaster, Female, Fertility, Longevity, Male, Metformin, Phosphorylation, Gene Expression, Drosophila Proteins, Lipid Metabolism, AMP-Activated Protein Kinases
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