If Started Early in Life, Metformin Treatment Increases Life Span and Postpones Tumors in Female SHR Mice
Open accessAbstract
Hyperglycemia and hyperinsulinemia accelerate both aging and cancer. Antidiabetic biguanides such as metformin decrease glucose, insulin and IGF-1 level. Metformin increases lifespan and prevents cancer in mice, although its effects vary, depending on mice strain and gender. Here we showed that chronic treatment of female outbred SHR mice with metformin started at the age of 3, 9 or 15 months decreased body temperature and postponed age-related switch-off of estrous function. Surprisingly, metformin did not affect levels of serum cholesterol, triglycerides, glucose and insulin. Treatment with metformin started at the age of 3 months increased mean life span by 14% and maximum life span by 1 month. The treatment started at the age of 9 months insignificantly increased mean life span by only 6%, whereas the treatment started at the age of 15 months failed to increase life span. The mean life span of tumor-free mice was increased by 21% in 'the youngest group', by 7% in 'middle-aged group' and in contrast was reduced by 13% in 'the oldest group'. When started at the age of 3 and 9 months, metformin delayed the first tumor detection by 22% and 25%, correspondingly. Thus, in female SHR mice, metformin increased life span and postponed tumors when started at the young and middle but not at the old age. In contrast, metformin improves reproductive function when started at any age.
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Despite activating AMPK, metformin has not reproducibly been shown to enhance lifespan in rodents and is notably less effective, or not effective, in older animals, including C. elegans.
“For instance, as discussed in the next section, despite activating AMPK, metformin has not reproducibly been shown to enhance lifespan in rodents and notably less, or not effective in older animals, including C. elegans (66, 72, 74, 75, 77, 78).”
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 [74]
This epidemiologic evidence has coalesced with experimental work in animals.
“This epidemiologic evidence has coalesced with experimental work in animals(256–263).”
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 [260]
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- Authors
- Anisimov, V. N., Berstein, L. M., Popovich, I. G., Zabezhinski, M. A., Egormin, P. A., Piskunova, T. S., Semenchenko, A. V., Tyndyk, M. L., Yurova, M. N., Kovalenko, I. G., & Poroshina, T. E.
- Affiliations
- Institute of Oncology NN Petrov (RU)
- N.N.Petrov Research Institute of Oncology, Pesochny-2, St.Petersburg 197758, Russia
- Corresponding author
- Anisimov, Vladimir N.
- Venue
- Aging
- Publisher
- Impact Journals, LLC
- Published
- 2011-02-21
- Volume
- 3
- Issue
- 2
- Pages
- 148-157
- ISSN
- 1945-4589 (ISSN-L)
- PMC
- PMC3082009
- OpenAlex
- W1500247249
- Cited by
- 285
- References
- 53
- Citations by year
- 2026: 5 · 2025: 15 · 2024: 14 · 2023: 16 · 2022: 25 · 2021: 16 · 2020: 23 · 2019: 23 · 2018: 21 · 2017: 17 · 2016: 13 · 2015: 14 · 2014: 23 · 2013: 26 · 2012: 24
- FWCI
- 10.77
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Aging (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Russian Foundation for Basic Research
- 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 extension, cancer prevention, biguanides, hyperinsulinemia, hyperglycemia, insulin-like growth factor I, reproductive function, tumor onset, age at treatment initiation, sex differences
- MeSH terms
- Age Factors, Animals, Body Temperature, Body Weight, Drinking, Eating, Female, Humans, Hypoglycemic Agents, Life Expectancy, Longevity, Metformin, Neoplasms, Estrous Cycle, Mice
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