Membrane particles from E. coli lacking the aroD gene extended worm lifespan by 29%
Membrane particles from E. coli lacking the aroD gene extended worm lifespan by 29%
On August 10, researchers described an experiment in an accepted article in npj Aging using membrane particles from E. coli cells lacking the aroD gene. Loss of this gene reduces the bacterial availability of a precursor needed to produce folate, or vitamin B9. The mean lifespan of C. elegans increased from 17.6 to 22.8 days.
The researchers selected aroD for this experiment based on a 2012 study, which linked deletion of the gene to longer lifespan in C. elegans and reduced bacterial folate synthesis. In the new experiment, the authors tested whether membrane particles isolated from the bacteria retained this effect.
To obtain the particles, the researchers disrupted cells from the mutant E. coli and the control strain BW25113, filtered the mixture, and centrifuged it twice at high speed. The worms received equal amounts of particles, with BW25113 serving as the control for the effect of aroD deletion. Adding PABA, a folate precursor, to the mutant bacterial culture eliminated the effect of its particles. Particles from normal E. coli treated with sulfamethoxazole, which blocks folate synthesis, produced a similar effect. Together, these experiments link the effect to bacterial folate synthesis.
The authors then moved from the particles to their contents. Among the small RNAs, which are short molecules that can alter gene activity, they identified Novel27 as a candidate. They placed synthetic Novel27 in particles from the control strain BW25113. In a separate experiment conducted in liquid medium, the worms lived for an average of 16.2 days instead of 12.2, an increase of 32.8%. This figure applies specifically to Novel27 delivered in control particles.
A computational analysis identified unc-13 as a possible target of Novel27. This gene is required for signal transmission between the worm's nerve cells. The level of unc-13 RNA decreased after Novel27 was added. When the authors separately suppressed this gene, mean lifespan increased from 11.5 to 12.6 days.