Aging, Age-Related Diseases, and the Zebrafish Model

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

In this review paper, the author elaborately described on the meachanism of aging, especially cellular snescence, and insisted the potential of zebrafish as a model animal for geroscience. The author introduces latest findings so that this paper would be helpful for many scientists who works on geroscience. 

On the other hand, this review paper is too long to grasp why zebrafish could be a nice model for geroscience. For example, the methodology part, "2.2. Senescence Detection Methods," would not be necessary for the aim of this review paper. This reviewer recommends to arrange this paper more concisely.

 

Author Response

We thank the reviewer for the comments. We appreciate that the reviewer points out that this review would be helpful to those looking at geroscience.

1. On the other hand, this review paper is too long to grasp why zebrafish could be a nice model for geroscience. For example, the methodology part, "2.2. Senescence Detection Methods," would not be necessary for the aim of this review paper. This reviewer recommends to arrange this paper more concisely.

We looked at where the paper could be condensed, and frankly, cannot find  much to cut out. The reviewer suggested cutting out all of 2.2, which is 3 pages, and while this is a lot, we feel that this section ties the parts of the paper together since we discuss markers that are primarily used in cell work, describe the methods used to look at aging/senescence, and cite these methods in whole or in part in the Zebrafish models portion.  We would like to keep this portion of the paper.

Reviewer 2 Report

Comments and Suggestions for Authors

The authors of this review investigated cellular aging. The aim of the review was to analyze cellular senescence and explore the use of the zebrafish (Danio rerio) as a model for studying aging and age-related diseases such as Alzheimer's disease. The findings highlight that the zebrafish, due to its genetic and structural similarities to humans, is a useful model for researching biomarkers of senescence and aging-related disorders.

 

In general the paper is well written and can be published after a review by the authors.

 

 

I suggest, the writing in italics of words that come from Latin would be:

row 170 in vitro

row 393 in vivo

 

row 62 "Many studies have identified different biomarkers that may have a link in aging and cellular senescence" - which are the studies? I recommend citing the studies to which reference was made.

line 123 "Regard less, senescence-associated β-galactosidase activity is the most widely used biomarker for senescence." - I recommend citing the source.

row 131 "The 131 more lipofuscin is present in the cell, the "older" the cell is said to be. As a result, lipofuscin 132 can be used as a biomarker for senescent cells." - I think the source should be cited.

The paragraph related to line 469, the cited source is missing.

The paragraphs related to lines 576-585 - the sources from where the ideas were taken are missing.

Also, as a general note, I suggest citing sources appropriately each time the information or idea is taken.

Author Response

We thank the reviewer for his/her criticisms. Our response is here.

1. I suggest, the writing in italics of words that come from Latin would be: row 170 in vitro, row 393 in vivo

Thank you for that observation. We have italicized the appropriate words.

2. row 62 "Many studies have identified different biomarkers that may have a link in aging and cellular senescence" - which are the studies? I recommend citing the studies to which reference was made.

Thank you for pointing this out. We have made the appropriate references to the work.

3. line 123 "Regard less, senescence-associated β-galactosidase activity is the most widely used biomarker for senescence." - I recommend citing the source.

This has been cited now.

4. row 131 "The 131 more lipofuscin is present in the cell, the "older" the cell is said to be. As a result, lipofuscin 132 can be used as a biomarker for senescent cells." - I think the source should be cited.

This has now been cited appropriately.

5. The paragraph related to line 469, the cited source is missing

Thank you. The reference is now included.

6. The paragraphs related to lines 576-585 - the sources from where the ideas were taken are missing.

Thank you. The reference is now included.

Reviewer 3 Report

Comments and Suggestions for Authors

The review article titled ‘Aging, Age-Related Diseases, and the Zebrafish Model’ by Abu-Dahech and Williams describes senescence markers and the benefits of using zebrafish as a senescence model. There are a few areas that need more detail and clarity to improve the quality of the manuscript:

 

1.     The major issue with the article is the title; although the authors have titled it "Aging, Age-Related Diseases," the article only discusses senescence. The authors should either change the title or include other factors of aging apart from senescence.

2.     There are several reviews available on senescence. The authors need to explain how this article is different or novel compared to published articles. They should focus more on how zebrafish is used as a senescence model rather than just discussing senescence markers and the zebrafish model.

3.     The authors need to include recent markers of senescence such as PAI-1 (Serpine1), GDF-15, uPAR, etc.

4.     They need to provide more details about senolytic treatments.

5.     The authors should explain how zebrafish act as a better animal model compared to mice based on lifespan.

Author Response

We thank the reviewer for the comments. We have tried to answer criticisms point by point  below.

1.     The major issue with the article is the title; although the authors have titled it "Aging, Age-Related Diseases," the article only discusses senescence. The authors should either change the title or include other factors of aging apart from senescence.

Thank you for the comment. To address this point, we have changed the title to "Senescence, Aging, Age-related diseases, and the Zebrafish model". We feel that this addresses the concerns along with also feeling that aging, age related diseases, and zebrafish have been adequately discussed.

2.     There are several reviews available on senescence. The authors need to explain how this article is different or novel compared to published articles. They should focus more on how zebrafish is used as a senescence model rather than just discussing senescence markers and the zebrafish model.

Thank you for this comment and an attempt to explain what we were thinking in writing this review. Reviews that we were able to find regarding aging, senescence while mentioning or using zebrafish are somewhat older. Perhaps 5-6 years old. Much has happened in that time, and we were trying to review what has happened in the zebrafish world and how the different techniques and models can and have been used in the last 5-6 years as well as maintaining a general review. We had no intention to discuss any one point at length, just to point out the various techniques and extrapolations that can drive the field forward with zebrafish.

3.     The authors need to include recent markers of senescence such as PAI-1 (Serpine1), GDF-15, uPAR, etc.

Thank you for  the comment. Serpine 1 was discussed in a paragraph including lines 790-791. More has been added along with two more references. 

4.     They need to provide more details about senolytic treatments.

Thanks for the comment. Senolytics were referenced in a paragraph in line 738-742 with one of the most recent references related to p21, transgenics, and selection of senolytics. This whole paragraph has been highlighted.

5.     The authors should explain how zebrafish act as a better animal model compared to mice based on lifespan.

While we did give the average age in line 648, we expanded this and added the average age of mice to the first part of the paragraph. This has been highlighted.

Round 2

Reviewer 3 Report

Comments and Suggestions for Authors

Authors need to change the title, as the article mainly mentions aging while the entire manuscript focuses on senescence. Since senescence is only one contributor to the aging process, either discuss aging and age-associated diseases in detail and connect them with senescence, or change the title to better reflect the article's content. 

Author Response

We would like to thank the reviewer for the comment.

Authors need to change the title, as the article mainly mentions aging while the entire manuscript focuses on senescence. Since senescence is only one contributor to the aging process, either discuss aging and age-associated diseases in detail and connect them with senescence, or change the title to better reflect the article's content. 

Thank you . We felt the same way about the original title that was "Aging, age-related diseases, and the Zebrafish model". We received another comment from a different reviewer requesting the change. We have changed the title back to the original one. Again, thank you