In summary, AOX expression did not consistently or significantly modify lifespan in Drosophila.
This demonstrates that proteomic approaches can be used to identify genes that modify lifespan.
DOI: http://dx.doi.org/10.7554/eLife.10181.041 10.7554/eLiFigure8 figureigure 8—figure supplement 3. Manipulating neurotransmission from primary olfactory neurons modifies lifespan.
Insulin/IGF like signaling is a key modulator of lifespan through its control of a transcriptional regulatory network and represents a potential target for miRNAs to modify lifespan.
DOI: http://dx.doi.org/10.7554/eLife.10181.040 10.7554/eLiFigure8 figureigure 8—figure supplement 2. Sorting animals based on their performance on salt chemotaxis and silencing primary neurons modifies lifespan.
Also, Durieux and colleagues have shown that manipulation of the electron transport chain only in neurons modifies lifespan of the worm [ 10].
Recent reports have demonstrated that in C. elegans miRNAs modify lifespan [ 17, 21, 22], although the mechanisms and direct biological targets of the miRNAs remain elusive.
Finally, daf-16 single mutants were modestly short-lived in comparison with wild-type (P < 0.001), consistent with previous reports (Kenyon et al., 1993; Lakowski & Hekimi, 1996; Lin et al., 2001; Larsen et al., 2005), and rbr-2 deficiency did not modify lifespan in a daf-16 background (P < 0.1).
To establish a high-confidence list of modifier genes, we considered significant only genes that modify life expectancy for more than the lifespan variance of Httex1p Q93-expressing flies between tubes within each trial.
The second complementary screen, using a library of flies with unique GS element insertions, identified genes, which when transcriptionally up- or downregulated modified the lifespan of flies expressing Aβ1 42.
In Mecp2−/y mice, ICM injection of the modified vector extended lifespan and was well tolerated by the liver but did not rescue RTT behavioral phenotypes.
