Metformin Retards Aging in C. elegans by Altering Microbial Folate and Methionine Metabolism

By F. Cabreiro, Catherine Au, K. Leung, Nuria Vergara-Irigaray, Helena M. Cochemé, Tahereh Noori, D. Weinkove, E. Schuster, N. Greene, D. Gems. Cell, 2013

919 citations recorded by the source corpus.

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. PaperClip

Subfields: Aging, Biological Psychiatry, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/2fe81ce626a7bc249c4f0d8a84740d7591e6d982

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Citations in the corpus

Metabolic Control of Longevity. (2016, background): “Metformin also affects folate and methionine metabolism in Escherichia coli, andC. elegans fed with metformin-treated bacteria experience methionine restriction and consequent lifespan extension (Cabreiro et al., 2013).”
The hallmarks of aging. (2013, background): “Recent studies have also shown that metformin retards aging in worms by impairing folate and methionine metabolism of their intestinal microbiome (Cabreiro et al., 2013).”
Metformin as a Tool to Target Aging (2016, positive): “In C. elegans metformin extends lifespan by several possible mechanisms including the alteration of the microbiome, specifically by changing microbial folate and methionine metabolism (Cabreiro et al., 2013).”
Metformin Is Associated With Higher Relative Abundance of Mucin-Degrading Akkermansia muciniphila and Several Short-Chain Fatty Acid–Producing Microbiota in the Gut (2016, neutral): “(28) first demonstrated that metformin impacts the”
The mechanisms of action of metformin (2017, background): “In the nematode worm, Caenorhabditis elegans, metformin lengthens lifespan through effects on intestinal microbial growth [49].”
The Mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance (2015, positive): “…terms of regulating glucose utilization, mitochondrial and fatty acid metabolism, and body weight (Ferguson et al., 2007), which is thought to occur by targeting the folate cycle (Cabreiro et al., 2013; Corominas-Faja et al., 2012) and signaling via cAMP (Miller et al., 2013) and AMPK (Shaw, 2013).”