Worms treated with metformin live longer. The drug may slow the aging process by mimicking the effects of dieting.
A recent study grew Caenorhabditis elegans worms in the presence of E.Coli bacteria and observed the effects of metformin on the aging process. The results showed the worms that were treated with metformin had lived longer when the E.Coli strain was sensitive to the medication. In fact, the metformin increased their lifespan by 6 days, which is one-third of their usual life expectancy.
The way that metformin slows the aging process is by changing the metabolism process in the bacteria. By doing so, the bacteria restrict the nutrients that are available to the worm. This process has a similar effect to diet restriction in the body.
To isolate the metabolic pathways affected by metformin, the researchers included strains of E.Coli that had defective genes linked to metabolism and controlled the levels of nutrients available to the bacteria. The results revealed that metformin disturbed the bacteria’s metabolism of folate and methionine. These are both building blocks to protein and any disruption can limit the nutrients that are available to the worm. This decrease in nutrients available to the host mimics diet restriction and allows the worm to live longer. However, when the worm was given excess sugar in its diet, the metformin did not delay the aging process.
In the gut, bacteria play an important role in nutrient digestion from food. Metabolic diseases including obesity, diabetes, inflammatory bowel disease, and cancer have been associated with defective gut bacteria. Even though metformin’s anti-aging mechanism has not been proven in humans, this study may lead to future ways of preventing metabolic diseases.
Metformin Retards Aging in C. elegans by Altering Microbial Folate and Methionine Metabolism. Cell, 2013; 153 (1): 228 DOI: 10.1016/j.cell.2013.02.035
ABSTRACTS
Metformin Retards Aging in C. elegans by Altering Microbial Folate and Methionine Metabolism
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Cell, Volume 153, Issue 1, 228-239, 28 March 2013
http://www.cell.com/retrieve/pii/S0092867413002675
Authors
Filipe Cabreiro, Catherine Au, Kit-Yi Leung, Nuria Vergara-Irigaray, Helena M. Cochemé, Tahereh Noori, David Weinkove, Eugene Schuster, Nicholas D.E. Greene, David Gemssend emailSee Affiliations
Highlights
The antidiabetic drug metformin disrupts bacterial folate and methionine cycles
This effect in C. elegans microbiota increases lifespan via methionine restriction
Metformin increases lifespan only if microbiota are present and is otherwise toxic
Microbiota may mediate metformin effects on mammalian health and aging
Summary
The biguanide drug metformin is widely prescribed to treat type 2 diabetes and metabolic syndrome, but its mode of action remains uncertain.
Metformin also increases lifespan in Caenorhabditis elegans cocultured with Escherichia coli. This bacterium exerts complex nutritional and pathogenic effects on its nematode predator/host that impact health and aging.
We report that metformin increases lifespan by altering microbial folate and methionine metabolism. Alterations in metformin-induced longevity by mutation of worm methionine synthase (metr-1) and S-adenosylmethionine synthase (sams-1) imply metformin-induced methionine restriction in the host, consistent with action of this drug as a dietary restriction mimetic. Metformin increases or decreases worm lifespan, depending on E. coli strain metformin sensitivity and glucose concentration. In mammals, the intestinal microbiome influences host metabolism, including development of metabolic disease.
Thus, metformin-induced alteration of microbial metabolism could contribute to therapeutic efficacy—and also to its side effects, which include folate deficiency and gastrointestinal upset.
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