Peer Review of “Roles of Progranulin and FRamides in Neural Versus Nonneural Tissues on Dietary Restriction–Related Longevity and Proteostasis in C. elegans (Preprint)”

This is a peer-review report submitted for the preprint “Roles of Progranulin and FRamides in Neural Versus Nonneural Tissues on Dietary Restriction–Related Longevity and Proteostasis in C. elegans.”

Round 1 Review

General Comments

Mir et al [1] is a study designed to understand the role of progranulin and FRamindes in neural and nonneural tissues through a dietary restriction approach.

The idea of using multiple mutants to understand the effect of flp-5, flp-14, flp-15, and pgrn-1 is interesting. While I like the overall idea and the experimental setup, I have a few questions regarding the study.

Specific Comments

1. I would have liked to see another control where wild-type worms were taken and heat treated at 35 °C alongside an unheated control group. This way I could have seen a more direct and indirect comparison between the groups.

2. I would have liked to understand the reason behind carrying out motility assays at 25 °C when the worms were maintained at 20 °C. Is it because it is ideal?

3. It could be that I might have read it wrong, but to me, the labels in Figures 1, 2, and S2 seem to be off. They don’t match the alphabetical order, or I might be missing something here.

4. For the motility assay, where they compared the GRU102 strain against GRU102 crossed with TU3335, I see that all the results were compared to one universal control. I would have liked to see mutant controls alongside the GRU102 and GRU102 crossed with TU3335. Again, by doing this, I would have had a direct comparison of the control, mutant controls, and mutants under conditions. Here, I cannot see how the mutants were performing on day 1 as the authors show the mutant data started from day 4.