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Open Access Highly Accessed Research article

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

Bhupinder Virk1, Gonçalo Correia123, David P Dixon12, Inna Feyst1, Jie Jia1, Nikolin Oberleitner1, Zoe Briggs1, Emily Hodge1, Robert Edwards12, John Ward4, David Gems5 and David Weinkove125*

Author affiliations

1 School of Biological and Biomedical Sciences, Durham University, South Road, Durham, DH1 3LE, UK

2 Biophysical Sciences Institute, Durham University, South Road, Durham, DH1 3LE, UK

3 Faculty of Science, University of Lisbon, Campo Grande, 1749-016, Lisbon, Portugal

4 Department of Structural and Molecular Biology, ISMB, University College London, London WC1E 6BT, UK

5 Institute of Healthy Ageing and Department of Genetics, Evolution and Environment, University College London, London WC1E 6BT, UK

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Citation and License

BMC Biology 2012, 10:67  doi:10.1186/1741-7007-10-67

Published: 31 July 2012

Abstract

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.

Keywords:
aging; microbes; folate; C. elegans; E. coli