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This is also true in Drosophila, where only homozygous, but not heterozygous Shaker mutants are short sleeping [ 1].
Therefore, it is possible that mev-1 mutants are short lived because of excessive ROS, which is similar to the conditions that decrease life span by treatment of high concentrations of ROS-generating chemicals [ 16, 45].
A primary argument for the latter is the fact that genetic manipulations increasing the antioxidative capacity do generally not increase lifespan, in fact, many oxidant-resistant mutants are short living [ 7, 8].
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We previously showed that ptl-1 mutants are short-lived (Chew et al., 2013, 2014).
In contrast, mev-1 respiratory chain mutants are short-lived and display an accelerated onset of branching.
It has previously been reported that mir-71 mutants are short-lived and that over-expression of mir-71 extended lifespan [ 17].
However, if sgk-1 null mutants are short-lived because they are sick, then sgk-1 gf) sgk-1 gfwould not be expected to live long.
skn-1 mutants are short-lived and exhibit sensitivity to oxidative stress, and overexpression of SKN-1 in intestinal cells increases lifespan and oxidative stress resistance [ 131- 133].
Since Atg7 mutants are short-lived, the deceleration of epidermal aging in this mutant suggests that in the epidermis healthspan can be uncoupled from longevity.
In C. elegans, SIR-2.1 activates DAF-16, and sir-2.1 mutants are short-lived and stress sensitive, while overexpression of sir-2.1 increases lifespan by 50% in a daf-16 dependent manner [ 86, 87].
However, sgk-1 null mutants are short-lived (Soukas et al., 2009; Alam et al., 2010; Chen et al., 2013; Xiao et al., 2013), and an sgk-1 gain-of-function (gf) mutant is long-lived (Chen et al., 2013).
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