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Metformin retards aging in C. elegans by altering microbial folate and methionine metabolism

Cabreiro, F.; Au, C.; Leung, K.-Y.; Vergara-Irigaray, N.; Cochemé, H.M.; Noori, T.; Weinkove, D.; Schuster, E.; Greene, N.D.E.; Gems, D.

Metformin retards aging in C. elegans by altering microbial folate and methionine metabolism Thumbnail


F. Cabreiro

C. Au

K.-Y. Leung

N. Vergara-Irigaray

H.M. Cochemé

T. Noori

E. Schuster

N.D.E. Greene

D. Gems


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.


Cabreiro, F., Au, C., Leung, K., Vergara-Irigaray, N., Cochemé, H., Noori, T., …Gems, D. (2013). Metformin retards aging in C. elegans by altering microbial folate and methionine metabolism. Cell, 153(1), 228-239.

Journal Article Type Article
Acceptance Date Feb 11, 2013
Publication Date Mar 28, 2013
Deposit Date Feb 11, 2013
Publicly Available Date Jul 27, 2015
Journal Cell
Print ISSN 0092-8674
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 153
Issue 1
Pages 228-239


Published Journal Article (944 Kb)

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