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The difference in the lifespan effects of the stc KG01230 mutation in unmated females compared to controls can be explained by differences in genetic background: in a long-lived background, the stc mutation decreased lifespan but had the opposite effect in a normal lifespan background.
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By contrast, expression of Ndi1, which bypasses (and also alleviates ROS production at) complex I (Sanz et al., 2010a), had only a negligible effect on female sterility (and lifespan), excluding background effects from the da-GAL4 driver or the w recipient that was used to generate the transgenic lines.
Notably, knockdown of daf-2 by dsRNA also increased lifespan in the background of adr-1 and adr-2 null mutations, resulting in a lifespan phenocopy similar to the wild type N2 worms (Figure 6a).
Overall, these data showed that in some genetic backgrounds there is correspondence between aggregation, cellular dysfunction, and lifespan, whereas other backgrounds appear to contain non-overlapping variation that uncouples aggregation from one or both measures of toxicity.
In fact, other previous works showed that, also in yeast, two-fold Sir2 overexpression does not extend lifespan in some backgrounds [ 46].
All together, these findings suggest that activation of IGF signaling is less affected in B6 IGF-1R+/− mice than in 129S2 IGF-1R+/− mice, which can explain the observed differences in lifespan extension between backgrounds.
In this study we present a comprehensive assessment of the SOD1 G93Adl mouse, and the effects of genetic background on lifespan, motor neuron and muscle function, and pathology.
As we found no effect of CR on rDNA silencing, we investigated whether deletion mutations that reproducibly extend lifespan in multiple yeast background strains alter rDNA silencing.
Invertebrate model species like yeast, worm and fly have been successfully used to study the genetic background of lifespan determination and ageing, leading to the identification of a number of relevant genes and pathways [ 1].
unc-43(n498), a gain-of-function allele (A ), and tax-6 ok2065), tax-6 ok2065e (B ), each extenull lifespallelethe WT Background and furtheachnhancextendedongevity of daf-2(RNAi) animalifespan
Male and female flies expressing RNAi against dFatp in the fat body displayed a significant lifespan extension compared to background controls (Fig. 2c,d, log-rank for males P = 0.002, females P < 0.0001).
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