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...

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Veröffentlicht in:Cell reports (Cambridge) 2016-02, Vol.14 (7), p.1611-1620
Hauptverfasser: Virk, Bhupinder, Jia, Jie, Maynard, Claire A., Raimundo, Adelaide, Lefebvre, Jolien, Richards, Shane A., Chetina, Natalia, Liang, Yen, Helliwell, Noel, Cipinska, Marta, Weinkove, David
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Sprache:eng
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Zusammenfassung: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. [Display omitted] •Limiting folate in E. coli, not in C. elegans, increases worm lifespan•An E. coli screen for worm longevity identifies folate synthesis as a target•Folate synthesis influences E. coli physiology independently of growth•Bacterial folate synthesis may be a sustainable target for chronic disease Virk et al. show that inhibiting E. coli folate synthesis does not increase C. elegans lifespan through changes to C. elegans folate, but by acting through an E. coli activity. They find nine E. coli mutants that extend lifespan. The gene identities suggest that mild bacterial toxicities accelerate host aging.
ISSN:2211-1247
2211-1247
DOI:10.1016/j.celrep.2016.01.051