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In particular, Forster et al. [46] reported a series of experiments in which long-term caloric restriction increased lifespan in B6 mice and B6D2F1 hybrids, but led to a slight lifespan decrease in mice of the DBA strain.
The slight lifespan lengthening of SJL/J mice under chronic irradiation that we observed in our last study could be explained by an adaptive response to radiation able to induce extended tumor latency as it has been described by Mitchel et al. (Mitchel et al. 1999; Mitchel et al. 2003; Mitchel et al. 2008).
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We detected a clear difference in age-dependent cognitive decline and a slight difference in lifespan (16% for median, 15% for maximum lifespan) between these lines.
GFP RNAi flies did show a slight decrease in lifespan as compared to matched controls (Fig. 4E-F), but the difference in median and maximum lifespan in comparison to their control counterparts was not statistically significant (Table 2).
We also noted a slight increase of lifespan in wild-type worms treated with ceh-18 RNAi (Table II), but this effect was not significant after controlling for multiple comparisons.
By contrast, in the presence of 50 mM metformin, 0.2 μg/ml TRI caused only a slight increase in lifespan (+8%, p < 0.001), whereas at higher concentrations it either had no effect (0.5 μg/ml TRI, −2%, p = 0.17) or reduced lifespan (1 μg/ml TRI, −19%, p < 0.001; Figure 4E).
In contrast, hMGS-wt induced a moderate reduction (mean survival = 31.2 days, n = 232, p < 1E-323, maximum survival = 45 days) and hMGS-9A(D) caused only a slight decrease in lifespan (mean survival = 37, n = 173, p = 8.3E-06, maximum survival = 55 days) when compared to control GFP-expressing flies (Fig 3A).
We also found that a single γ-ray exposure at the similar dose and dose rate did not cause life shortening, but rather led to a slight extension of their lifespan.
Methionine restriction also causes a slight decrease in the average lifespan but does not affect reproductive fitness in Drosophila (Zajitschek et al., 2013).
A relation between the two would explain the slight, less significant difference in lifespan at 20°, when only ∼20% of the mir-83 (n4638 ); mir-34 (gk437 ) population is migration defective, vs. the significant difference in lifespan when animals undergo temperature changes, as now ∼60% of the population is migration defective.
The few dKO mice injected with less than 5E + 12 vg displayed very low levels of dystrophin expression and only showed a very slight improvement of their phenotype and lifespan.
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Justyna Jupowicz-Kozak
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