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Excessive folate synthesis limits lifespan in the C. elegans: E. coli aging model

Virk, B; Correia, G; Dixon, DP; Feyst, I; Jia, J; Oberleitner, N; Briggs, Z; Hodge, E; Edwards, R; Ward, J; Gems, D; Weinkove, D

Excessive folate synthesis limits lifespan in the C. elegans: E. coli aging model Thumbnail


B Virk

G Correia

DP Dixon

I Feyst

J Jia

N Oberleitner

Z Briggs

E Hodge

R Edwards

J Ward

D Gems


Background: Gut microbes influence animal health and thus, are potential targets for interventions that slow aging. Live E. coli provides the nematode worm Caenorhabditis elegans with vital micronutrients, such as folates that cannot be synthesized by animals. However, the microbe also limits C. elegans lifespan. Understanding these interactions may shed light on how intestinal microbes influence mammalian aging. Results: Serendipitously, we isolated an E. coli mutant that slows C. elegans aging. We identified the disrupted gene to be aroD, which is required to synthesize aromatic compounds in the microbe. Adding back aromatic compounds to the media revealed that the increased C. elegans lifespan was caused by decreased availability of para-aminobenzoic acid, a precursor to folate. Consistent with this result, inhibition of folate synthesis by sulfamethoxazole, a sulfonamide, led to a dose-dependent increase in C. elegans lifespan. As expected, these treatments caused a decrease in bacterial and worm folate levels, as measured by mass spectrometry of intact folates. The folate cycle is essential for cellular biosynthesis. However, bacterial proliferation and C. elegans growth and reproduction were unaffected under the conditions that increased lifespan. Conclusions: In this animal:microbe system, folates are in excess of that required for biosynthesis. This study suggests that microbial folate synthesis is a pharmacologically accessible target to slow animal aging without detrimental effects.


Virk, B., Correia, G., Dixon, D., Feyst, I., Jia, J., Oberleitner, N., …Weinkove, D. (2012). Excessive folate synthesis limits lifespan in the C. elegans: E. coli aging model. BMC Biology, 10(1), Article 67.

Journal Article Type Article
Publication Date Jul 1, 2012
Deposit Date Aug 3, 2012
Publicly Available Date Sep 14, 2012
Journal BMC Biology
Publisher BioMed Central
Peer Reviewed Peer Reviewed
Volume 10
Issue 1
Article Number 67


Published Journal Article (775 Kb)

Copyright Statement
© 2012 Virk et al; licensee BioMed Central Ltd. <br /> This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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