Metformin Retards Aging in C. elegans by Altering Microbial Folate and Methionine Metabolism
File(s)
Published version
Author(s)
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.
Date Issued
2013-03-28
Date Acceptance
2013-02-11
Citation
Cell, 2013, 153 (1), pp.228-239
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.
License URL
Subjects
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
Developmental Biology
06 Biological Sciences
11 Medical And Health Sciences
Publication Status
Published