Mechanisms of Life Span Extension by Rapamycin in the Fruit Fly Drosophila Melanogaster
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The target of rapamycin (TOR) pathway is a major nutrient-sensing pathway that, when genetically downregulated, increases life span in evolutionarily diverse organisms including mammals. The central component of this pathway, TOR kinase, is the target of the inhibitory drug rapamycin, a highly specific and well-described drug approved for human use. We show here that feeding rapamycin to adult Drosophila produces the life span extension seen in some TOR mutants. Increase in life span by rapamycin was associated with increased resistance to both starvation and paraquat. Analysis of the underlying mechanisms revealed that rapamycin increased longevity specifically through the TORC1 branch of the TOR pathway, through alterations to both autophagy and translation. Rapamycin could increase life span of weak insulin/Igf signaling (IIS) pathway mutants and of flies with life span maximized by dietary restriction, indicating additional mechanisms.
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Metformin, like rapamycin, is known to inhibit mTOR signaling.
“Of significance is that metformin, like rapamycin, is known to inhibit mTOR signaling, and the inhibition of the mTOR signaling pathway with rapamycin has been shown to extend lifespan in C. elegans, S. cerevisiae, and Drosophila melanogaster (fruit fly) (221–225).”
From A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan (2021) · cites this paper as [222]
Inhibition of the mTOR signaling pathway with rapamycin has been shown to extend lifespan in C. elegans, S. cerevisiae, and Drosophila melanogaster.
“Of significance is that metformin, like rapamycin, is known to inhibit mTOR signaling, and the inhibition of the mTOR signaling pathway with rapamycin has been shown to extend lifespan in C. elegans, S. cerevisiae, and Drosophila melanogaster (fruit fly) (221–225).”
From A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan (2021) · cites this paper as [222]
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- Authors
- Bjedov, I., Toivonen, J. M., Kerr, F., Slack, C., Jacobson, J., Foley, A., & Partridge, L.
- Affiliations
- University College London (GB)
- Max Planck Institute for Biology of Ageing (DE)
- Corresponding author
- Partridge, Linda
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2010-01
- Volume
- 11
- Issue
- 1
- Pages
- 35-46
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC2824086
- OpenAlex
- W2065197926
- Cited by
- 1,057
- References
- 63
- Citations by year
- 2026: 40 · 2025: 55 · 2024: 61 · 2023: 75 · 2022: 64 · 2021: 73 · 2020: 72 · 2019: 76 · 2018: 64 · 2017: 60 · 2016: 66 · 2015: 66 · 2014: 73 · 2013: 68 · 2012: 63
- FWCI
- 23.10
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ResearchOnline (Glasgow Caledonian University) (acceptedVersion, cc-by)
- Aston Publications Explorer (Aston University) (submittedVersion)
- Edinburgh Napier Research Repository (Edinburgh Napier University) (submittedVersion, cc-by)
- UCL Discovery (University College London) (submittedVersion)
- Max Planck Digital Library (submittedVersion)
- Research Output (Edinburgh Napier University) (submittedVersion, cc-by)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Warwick Research Archive Portal (University of Warwick) (submittedVersion)
- Funders
- Wellcome Trust
- European Commission
- Directorate for Biological Sciences
- 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 › PI3K/AKT/mTOR signaling in cancer
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- rapamycin, lifespan extension, TOR signaling, TORC1, Drosophila melanogaster, longevity, autophagy, translational regulation, insulin/IGF-1 signaling, dietary restriction, starvation resistance, paraquat resistance, nutrient sensing
- MeSH terms
- Aging, Animals, Autophagy, Drosophila melanogaster, Longevity, Phosphorylation, Protein Kinases, Protein Biosynthesis, Ribosomal Protein S6 Kinases, Sirolimus, Drosophila Proteins, Proto-Oncogene Proteins c-akt, TOR Serine-Threonine Kinases
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