Metformin Supplementation and Life Span in Fischer-344 Rats
Open accessAbstract
Calorie restriction (CR) has been known for more than 70 years to extend life span and delay disease in rodent models. Metformin administration in rodent disease models has been shown to delay cancer incidence and progression, reduce cardiovascular disease and extend life span. To more directly test the potential of metformin supplementation (300 mg/kg/day) as a CR mimetic, life-span studies were performed in Fischer-344 rats and compared with ad libitum feeding and CR (30%). The CR group had significantly reduced food intake and body weight throughout the study. Body weight was significantly reduced in the metformin group compared with control during the middle of the study, despite similar weekly food intake. Although CR significantly extended early life span (25th quantile), metformin supplementation did not significantly increase life span at any quantile (25th, 50th, 75th, or 90th), overall or maximum life span (p > .05) compared with control.
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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 [78]
Smith et al. concluded that metformin is not a calorie restriction mimetic (CRM).
“Smith et al. have demonstrated that calorie restriction, but not metformin (in the diet 300 mg/kg/day), extended lifespan in male Fisher-344 rats, leading to the conclusion that metformin is not a calorie restriction mimetic (CRM) (78) (see Table 1 for a summary).”
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 [78]
Smith et al. demonstrated that calorie restriction, but not metformin (in the diet 300 mg/kg/day), extended lifespan in male Fisher-344 rats.
“Smith et al. have demonstrated that calorie restriction, but not metformin (in the diet 300 mg/kg/day), extended lifespan in male Fisher-344 rats, leading to the conclusion that metformin is not a calorie restriction mimetic (CRM) (78) (see Table 1 for a summary).”
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 [78]
If we accept that metformin, despite inhibiting mTOR, is not a CRM, then metformin would not be expected to extend lifespan.
“If we accept this argument and also accept that metformin, despite inhibiting mTOR, is not a CRM (77, 78) then metformin would not be expected to extend lifespan.”
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 [78]
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- Authors
- Smith, D. L., Elam, C. F., Mattison, J. A., Lane, M. A., Roth, G. S., Ingram, D. K., & Allison, D. B.
- Affiliations
- University of Alabama at Birmingham (US)
- National Institutes of Health (US)
- Pennington Biomedical Research Center (US)
- Venue
- The Journals of Gerontology Series A: Biological Sciences and Medical Sciences
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-03-19
- Volume
- 65A
- Issue
- 5
- Pages
- 468-474
- ISSN
- 1079-5006 (ISSN-L)
- 1758-535X
- PMC
- PMC2854888
- OpenAlex
- W2141060438
- Cited by
- 153
- References
- 49
- Citations by year
- 2025: 6 · 2024: 9 · 2023: 10 · 2022: 9 · 2021: 8 · 2020: 11 · 2019: 14 · 2018: 10 · 2017: 3 · 2016: 16 · 2015: 11 · 2014: 10 · 2013: 7 · 2012: 12
- FWCI
- 3.96
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journals of Gerontology Series A (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging
- National Heart, Lung, and Blood Institute (T32HL079888)
- National Institute of Diabetes and Digestive and Kidney Diseases (T32DK062710)
- 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
- Health Sciences › Medicine › Physiology › Dietary Effects on Health
- Keywords
- metformin, caloric restriction, lifespan extension, F344 rats, body weight, dietary intake, aging, longevity
- MeSH terms
- Animals, Blood Glucose, Body Temperature, Body Weight, Eating, Food Additives, Hypoglycemic Agents, Insulin, Longevity, Male, Metformin, Rats, Inbred F344, Rats
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