title: Folate Acts in E. coli to Accelerate C. elegans Aging Independently of Bacterial Biosynthesis.
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.
authors.affiliation: School of Biological and Biomedical Sciences, Durham University, South Road, Durham DH1 3LE, UK.
authors.forename: Bhupinder
authors.initials: B
authors.lastname: Virk
authors.affiliation: School of Biological and Biomedical Sciences, Durham University, South Road, Durham DH1 3LE, UK; Department of Nutrition, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai Institute for Pediatric Research, Shanghai 200092, China; Department of Clinical Nutrition, Xin Hua Hospital affiliated to SJTU School of Medicine, Shanghai 200092, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Jia
authors.affiliation: School of Biological and Biomedical Sciences, Durham University, South Road, Durham DH1 3LE, UK.
authors.forename: Claire A
authors.initials: CA
authors.lastname: Maynard
authors.affiliation: School of Biological and Biomedical Sciences, Durham University, South Road, Durham DH1 3LE, UK.
authors.forename: Adelaide
authors.initials: A
authors.lastname: Raimundo
authors.affiliation: School of Biological and Biomedical Sciences, Durham University, South Road, Durham DH1 3LE, UK; Department HIVB, VIVES, Wilgenstraat 32, 8800 Roeselare, Belgium.
authors.forename: Jolien
authors.initials: J
authors.lastname: Lefebvre
authors.affiliation: School of Biological and Biomedical Sciences, Durham University, South Road, Durham DH1 3LE, UK.
authors.forename: Shane A
authors.initials: SA
authors.lastname: Richards
authors.affiliation: School of Biological and Biomedical Sciences, Durham University, South Road, Durham DH1 3LE, UK.
authors.forename: Natalia
authors.initials: N
authors.lastname: Chetina
authors.affiliation: School of Biological and Biomedical Sciences, Durham University, South Road, Durham DH1 3LE, UK.
authors.forename: Yen
authors.initials: Y
authors.lastname: Liang
authors.affiliation: School of Biological and Biomedical Sciences, Durham University, South Road, Durham DH1 3LE, UK.
authors.forename: Noel
authors.initials: N
authors.lastname: Helliwell
authors.affiliation: School of Biological and Biomedical Sciences, Durham University, South Road, Durham DH1 3LE, UK; Biophysical Sciences Institute, Durham University, South Road, Durham DH1 3LE, UK.
authors.forename: Marta
authors.initials: M
authors.lastname: Cipinska
authors.affiliation: School of Biological and Biomedical Sciences, Durham University, South Road, Durham DH1 3LE, UK; Biophysical Sciences Institute, Durham University, South Road, Durham DH1 3LE, UK. Electronic address: david.weinkove@durham.ac.uk.
authors.forename: David
authors.initials: D
authors.lastname: Weinkove
mesh_terms: D010129:4-Aminobenzoic Acid / Q000378:metabolism; D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D005492:Folic Acid / Q000096:biosynthesis*; D005786:Gene Expression Regulation; D043425:Glutamate Carboxypeptidase II / Q000172:deficiency / Q000235:genetics; D054884:Host-Pathogen Interactions; D002955:Leucovorin / Q000494:pharmacology; D008136:Longevity / Q000235:genetics; D064307:Microbiota / Q000502:physiology; D027361:Organic Anion Transporters / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013420:Sulfamethoxazole / Q000494:pharmacology; D015996:Survival Rate
chemical_list: D000900:Anti-Bacterial Agents; D029742:Caenorhabditis elegans Proteins; C550335:Folt-1 protein, C elegans; D027361:Organic Anion Transporters; D005492:Folic Acid; D043425:Glutamate Carboxypeptidase II; D013420:Sulfamethoxazole; D002955:Leucovorin; D010129:4-Aminobenzoic Acid