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

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Title: Metformin Retards Aging in C. elegans by Altering Microbial Folate and Methionine Metabolism
Author(s): Cabreiro, F
Au, C
Leung, KY
Vergara-Irigaray, N
Cochemé, HM
Noori, T
Weinkove, D
Schuster, E
Greene, ND
Gems, D
Item Type: Journal Article
Abstract: 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.
Publication Date: 28-Mar-2013
Date of Acceptance: 11-Feb-2013
URI: http://hdl.handle.net/10044/1/40463
DOI: http://dx.doi.org/10.1016/j.cell.2013.02.035
ISSN: 1097-4172
Publisher: Elsevier
Start Page: 228
End Page: 239
Journal / Book Title: Cell
Volume: 153
Issue: 1
Copyright Statement: Open access under CC BY license.
Keywords: Adenylate Kinase
Aging
Animals
Biguanides
Caenorhabditis elegans
Caenorhabditis elegans Proteins
Caloric Restriction
DNA-Binding Proteins
Diabetes Mellitus, Type 2
Escherichia coli
Folic Acid
Humans
Hypoglycemic Agents
Longevity
Metagenome
Metformin
Methionine
Transcription Factors
Animals
Humans
Caenorhabditis elegans
Escherichia coli
Diabetes Mellitus, Type 2
Biguanides
Metformin
Folic Acid
Adenylate Kinase
Methionine
DNA-Binding Proteins
Caenorhabditis elegans Proteins
Transcription Factors
Hypoglycemic Agents
Caloric Restriction
Aging
Longevity
Metagenome
Developmental Biology
06 Biological Sciences
11 Medical And Health Sciences
Publication Status: Published
Appears in Collections:Clinical Sciences
Molecular Sciences
Faculty of Medicine



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