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Live\n                      <jats:italic>E. coli<\/jats:italic>\n                      provides the nematode worm\n                      <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                      with vital micronutrients, such as folates that cannot be synthesized by animals. However, the microbe also limits\n                      <jats:italic>C. elegans<\/jats:italic>\n                      lifespan. Understanding these interactions may shed light on how intestinal microbes influence mammalian aging.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Serendipitously, we isolated an\n                      <jats:italic>E. coli<\/jats:italic>\n                      mutant that slows\n                      <jats:italic>C. elegans<\/jats:italic>\n                      aging. We identified the disrupted gene to be\n                      <jats:italic>aroD<\/jats:italic>\n                      , which is required to synthesize aromatic compounds in the microbe. Adding back aromatic compounds to the media revealed that the increased\n                      <jats:italic>C. elegans<\/jats:italic>\n                      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\n                      <jats:italic>C. elegans<\/jats:italic>\n                      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\n                      <jats:italic>C. elegans<\/jats:italic>\n                      growth and reproduction were unaffected under the conditions that increased lifespan.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats: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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/1741-7007-10-67","type":"journal-article","created":{"date-parts":[[2012,7,31]],"date-time":"2012-07-31T06:16:00Z","timestamp":1343715360000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":112,"title":["Excessive folate synthesis limits lifespan in the C. elegans: E. coliaging model"],"prefix":"10.1186","volume":"10","author":[{"given":"Bhupinder","family":"Virk","sequence":"first","affiliation":[]},{"given":"Gon\u00e7alo","family":"Correia","sequence":"additional","affiliation":[]},{"given":"David P","family":"Dixon","sequence":"additional","affiliation":[]},{"given":"Inna","family":"Feyst","sequence":"additional","affiliation":[]},{"given":"Jie","family":"Jia","sequence":"additional","affiliation":[]},{"given":"Nikolin","family":"Oberleitner","sequence":"additional","affiliation":[]},{"given":"Zoe","family":"Briggs","sequence":"additional","affiliation":[]},{"given":"Emily","family":"Hodge","sequence":"additional","affiliation":[]},{"given":"Robert","family":"Edwards","sequence":"additional","affiliation":[]},{"given":"John","family":"Ward","sequence":"additional","affiliation":[]},{"given":"David","family":"Gems","sequence":"additional","affiliation":[]},{"given":"David","family":"Weinkove","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2012,7,31]]},"reference":[{"key":"583_CR1","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1007\/s10522-011-9352-5","volume":"12","author":"E Ottaviani","year":"2011","unstructured":"Ottaviani E, Ventura N, Mandrioli M, Candela M, Franchini A, Franceschi C: Gut microbiota as a candidate for lifespan extension: an ecological\/evolutionary perspective targeted on living organisms as metaorganisms. 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