Reference - Detail
|Author||Virk B, Jia J, Maynard CA, Raimundo A, Lefebvre J, Richards SA, Chetina N, Liang Y, Helliwell N, Cipinska M, Weinkove D.|
|Title||Folate Acts in E. coli to Accelerate C. elegans Aging Independently of Bacterial Biosynthesis.|
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.
|MeSH||4-Aminobenzoic Acid / metabolism Aging / genetics Aging / metabolism* Animals Anti-Bacterial Agents / pharmacology Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans / microbiology Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Escherichia coli / drug effects Escherichia coli / growth & development Escherichia coli / metabolism* Folic Acid / biosynthesis* Gene Expression Regulation Glutamate Carboxypeptidase II / deficiency Glutamate Carboxypeptidase II / genetics Host-Pathogen Interactions* Leucovorin / pharmacology Longevity / genetics Microbiota / physiology Organic Anion Transporters / genetics Organic Anion Transporters / metabolism Signal Transduction Sulfamethoxazole / pharmacology Survival Rate|
|Prokaryotes E. coli|