PONE-D-23-19389Age-related changes in dermal collagen physical properties in human skinPLOS ONE

Dear Dr. Quan,

This is to inform you that your manuscript "Age-related changes in dermal collagen physical properties in human skin" requires a minor revision. Your manuscript was reviewed by expert referees who have made a number of recommendations regarding the suitability of your paper for publication in the PLOS ONE. The reviewers’ comments are provided below for your assistance in revising the paper. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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Nileshkumar Dubey

Academic Editor

PLOS ONE

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Reviewers' comments:

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Comments to the Author

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Reviewer #1: Yes

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Authors have drafted interesting piece of work which well aligned and well addressed.

Data of manuscript has been well articulated and hypothesis has well explained which fluently understandable by readers.

1. I recommend authors to go through entire manuscript once more for minor grammatical errors. I recommend to1

change term Organ culture to Organotypic culture, to show the skin biopies were cultured and maintained under in vitro conditions.

2. Authors are recommended toreplace old citation and cite recently published articles and to stick max 5 years old references only. ( 2018-2023).

Reviewer #2: Authors tried to clarify the age-related changes in dermal collagen physical properties (surface roughness, stiffness, and hardness) using atomic force microscopy (AFM) and nanoindentation. They found that in the aged dermis, the surface of collagen fibrils was rougher, and fiber bundles were stiffer and harder, compared to young dermal collagen and that the age-related elevation of matrix metalloproteinase-1 (MMP-1) and advanced glycation end products (AGEs) might be responsible for rougher and stiffer/harder dermal collagen, respectively. These findings are interesting but there are some points to improve this paper.

Comment 1

Although some studies have already been carried out to clarify the age-related changes in dermal collagen physical properties by using atomic force microscopy (AFM) and nanoindentation, authors did not describe these works in the introduction, Authors should describe them and emphasize the importance of this work.

Comment 2

In histology and morphometry (Page7), a scale of 1-9 for each parameter was used for the analysis. However, they did not describe the details of the difference of 1 to 9 scales. To understand the importance of Fig. 1b, they should show the differences of scales in thinness, space, and disorganization of dermal collagen fibers.

Comment 3

In Figs 3 and 4, in addition to AFM data, skin section data should be necessary to be shown as the effects of MMP-1 digestion and ribose crossing on the dermis. Moreover, for Fig. 4, the presence of a glycated collagen matrix should be shown by histological immunostaining.

Comment 4

In the paper, published in International Journal of Nanomedicine 2017:12 3303–3314, “Combining nano-physical and computational investigations to understand the nature of “aging” in dermal collagen”, an age-related decrease in the Young’s modulus of the transverse fibril (from 8.11 to 4.19 GPa in young to old volunteers, respectively, P,0.001) was reported. Authors should discuss the discrepancy.

Comment 5

In Figs 3c and 4c, the spelling of punch in “Young skin puch biopsy” should be corrected.

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Reviewer #1: Yes: HARISH KIRAN HANDRAL

Reviewer #2: No

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Age-related changes in dermal collagen physical properties in human skin

PONE-D-23-19389R1

Dear Dr. Quan,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Nileshkumar Dubey

Academic Editor

PLOS ONE

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Reviewers' comments: