Cabreiro, F. and Au, C. and Leung, K.-Y. and Vergara-Irigaray, N. and Cochemé, H.M. and Noori, T. and Weinkove, D. and Schuster, E. and Greene, N.D.E. and Gems, D. (2013) 'Metformin retards aging in C. elegans by altering microbial folate and methionine metabolism.', Cell., 153 (1). pp. 228-239.
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.
|Full text:||(VoR) Version of Record|
Available under License - Creative Commons Attribution.
Download PDF (923Kb)
|Publisher Web site:||http://dx.doi.org/10.1016/j.cell.2013.02.035|
|Publisher statement:||Open access under CC BY license. This article is available under the terms of the Creative Commons Attribution License (CC BY). You may distribute and copy the article, create extracts, abstracts, and other revised versions, adaptations or derivative works of or from an article (such as a translation), to include in a collective work (such as an anthology), to text or data mine the article, including for commercial purposes without permission from Elsevier. The original work must always be appropriately credited.|
|Date accepted:||11 February 2013|
|Date deposited:||27 July 2015|
|Date of first online publication:||March 2013|
|Date first made open access:||No date available|
Save or Share this output
|Look up in GoogleScholar|