Effect of metformin on life span and on the development of spontaneous mammary tumors in HER-2/neu transgenic mice
Abstract
Studies in mammals have led to the suggestion that hyperglycemia and hyperinsulinemia are important factors both in aging and in the development of cancer. Insulin/insulin-like growth factor 1 (IGF-1) signaling molecules that have been linked to longevity include DAF-2 and InR and their homologues in mammals, and inactivation of the corresponding genes is followed by increased life span in nematodes, fruit flies and mice. It is possible that the life-prolonging effects of calorie restriction are due to decreasing IGF-1 levels. A search of pharmacological modulators of insulin/IGF-1 signaling pathway (which mimetic effects of life span extending mutations or calorie restriction) could be a perspective direction in regulation of longevity. The chronic treatment of female transgenic HER-2/neu mice with metformin (100 mg/kg in drinking water) slightly decreased the food consumption but failed in reducing the body weight or temperature, slowed down the age-related rise in blood glucose and triglycerides level, as well as the age-related switch-off of estrous function, prolonged the mean life span by 8% (p < 0.05), the mean life span of last 10% survivors by 13.1%, and the maximum life span by 1 month in comparison with control mice. The demographic aging rate represented by the estimate of respective Gompertz's parameter was decreased 2.26 times. The metformin-treatment significantly decreased the incidence and size of mammary adenocarcinomas in mice and increased the mean latency of the tumors.
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This epidemiologic evidence has coalesced with experimental work in animals.
“This epidemiologic evidence has coalesced with experimental work in animals(256–263).”
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Metformin reduces mammary tumor growth in rodent models.
“Metformin has also been shown to reduce mammary tumor growth in rodent models (88).”
From Diabetes and Cancer (2010) · cites this paper as [88]
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- Authors
- Anisimov, V. N., Berstein, L. M., Egormin, P. A., Piskunova, T. S., Popovich, I. G., Zabezhinski, M. A., Kovalenko, I. G., Poroshina, T. E., Semenchenko, A. V., Provinciali, M., Re, F., & Franceschi, C.
- Affiliations
- Institute of Oncology NN Petrov (RU)
- Istituto Nazionale di Riposo e Cura per Anziani (IT)
- University of Bologna (IT)
- Corresponding author
- Anisimov, Vladimir N.
- ORCID
- Venue
- Experimental Gerontology
- Publisher
- Elsevier BV
- Published
- 2005-08
- Volume
- 40
- Issue
- 8-9
- Pages
- 685-693
- ISSN
- 0531-5565 (ISSN-L)
- OpenAlex
- W2030031350
- Cited by
- 402
- References
- 53
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 11 · 2023: 15 · 2022: 11 · 2021: 19 · 2020: 22 · 2019: 19 · 2018: 15 · 2017: 19 · 2016: 18 · 2015: 26 · 2014: 41 · 2013: 28 · 2012: 26
- FWCI
- 2.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Gerontology (publishedVersion)
- PubMed (publishedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Physiology › Dietary Effects on Health
- Keywords
- metformin, lifespan, mammary adenocarcinoma, insulin/IGF-1 signaling, longevity, caloric restriction mimetics, hyperglycemia, hyperinsulinemia, tumor latency
- MeSH terms
- Adenocarcinoma, Aging, Animals, Blood Glucose, Body Temperature, Body Weight, Estrus, Female, Hypoglycemic Agents, Insulin, Lipoproteins, LDL, Longevity, Membrane Glycoproteins, Metformin, Mice, Transgenic, RNA, Messenger, Serine Endopeptidases, Thyroxine, Triglycerides, Triiodothyronine, Mammary Neoplasms, Animal, Receptor, ErbB-2, Erb-b2 Receptor Tyrosine Kinases, Reverse Transcriptase Polymerase Chain Reaction, Mice, Pore Forming Cytotoxic Proteins, Granzymes, Perforin
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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