Abstract
Folates are cofactors for biosynthetic enzymes in all eukaryotic and prokaryotic cells. Animals cannot synthesize folate and must acquire it from their diet or microbiota. Previously, we showed that inhibiting E. coli folate synthesis increases C. elegans lifespan. Here, we show that restriction or supplementation of C. elegans folate does not influence lifespan. Thus, folate is required in E. coli to shorten worm lifespan. Bacterial proliferation in the intestine has been proposed as a mechanism for the life-shortening influence of E. coli. However, we found no correlation between C. elegans survival and bacterial growth in a screen of 1,000+ E. coli deletion mutants. Nine mutants increased worm lifespan robustly, suggesting specific gene regulation is required for the life-shortening activity of E. coli. Disrupting the biosynthetic folate cycle did not increase lifespan. Thus, folate acts through a growth-independent route in E. coli to accelerate animal aging.
Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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4-Aminobenzoic Acid / metabolism
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Aging / genetics
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Aging / metabolism*
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Animals
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Anti-Bacterial Agents / pharmacology
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Caenorhabditis elegans / genetics
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Caenorhabditis elegans / metabolism*
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Caenorhabditis elegans / microbiology
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Caenorhabditis elegans Proteins / genetics
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Caenorhabditis elegans Proteins / metabolism
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Escherichia coli / drug effects
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Escherichia coli / growth & development
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Escherichia coli / metabolism*
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Folic Acid / biosynthesis*
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Gene Expression Regulation
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Glutamate Carboxypeptidase II / deficiency
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Glutamate Carboxypeptidase II / genetics
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Host-Pathogen Interactions*
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Leucovorin / pharmacology
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Longevity / genetics
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Microbiota / physiology
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Organic Anion Transporters / genetics
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Organic Anion Transporters / metabolism
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Signal Transduction
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Sulfamethoxazole / pharmacology
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Survival Rate
Substances
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Anti-Bacterial Agents
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Caenorhabditis elegans Proteins
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Folt-1 protein, C elegans
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Organic Anion Transporters
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Folic Acid
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Glutamate Carboxypeptidase II
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Sulfamethoxazole
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Leucovorin
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4-Aminobenzoic Acid