Excessive folate synthesis limits lifespan in the <it>C. elegans</it>: <it>E. coli </it>aging model

• Main Authors: Virk Bhupinder, Correia Gonçalo, Dixon David P, Feyst Inna, Jia Jie, Oberleitner Nikolin, Briggs Zoe, Hodge Emily, Edwards Robert, Ward John, Gems David, Weinkove David
• Format: Article
• Language: English
• Published: BMC 2012-07-01
• Series: BMC Biology
• Subjects: aging; microbes; folate; <it>C. elegans</it>; <it>E. coli</it>
• Online Access: http://www.biomedcentral.com/1741-7007/10/67

<p>Abstract</p> <p>Background</p> <p>Gut microbes influence animal health and thus, are potential targets for interventions that slow aging. Live <it>E. coli </it>provides the nematode worm <it>Caenorhabditis elegans </it>with vital micronutrients, such as folates that cannot be synthesized by animals. However, the microbe also limits <it>C. elegans </it>lifespan. Understanding these interactions may shed light on how intestinal microbes influence mammalian aging.</p> <p>Results</p> <p>Serendipitously, we isolated an <it>E. coli </it>mutant that slows <it>C. elegans </it>aging. We identified the disrupted gene to be <it>aroD</it>, which is required to synthesize aromatic compounds in the microbe. Adding back aromatic compounds to the media revealed that the increased <it>C. elegans </it>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 <it>C. elegans </it>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 <it>C. elegans </it>growth and reproduction were unaffected under the conditions that increased lifespan.</p> <p>Conclusions</p> <p>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.</p>