Virk, B. and Correia, G. and Dixon, D.P. and Feyst, I. and Jia, J. and Oberleitner, N. and Briggs, Z. and Hodge, E. and Edwards, R. and Ward, J. and Gems, D. and Weinkove, D. (2012) 'Excessive folate synthesis limits lifespan in the C. elegans : E. coli aging model.', BMC biology., 10 (1). p. 67.
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.
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|Publisher Web site:||http://dx.doi.org/10.1186/1741-7007-10-67|
|Publisher statement:||© 2012 Virk et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.|
|Date accepted:||No date available|
|Date deposited:||14 September 2012|
|Date of first online publication:||July 2012|
|Date first made open access:||No date available|
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