Cosmeceuticals for Anti-Aging: Mechanisms, Clinical Evidence, and Regulatory Insights—A Comprehensive Review

Comments 1: References do not match with text and cited at the end (for example: reference no65, 66, 67 etc.). Kindly cross checks all references.

Response 1: Thank you for pointing this out. We agree with this comment. Therefore, we carefully re-checked all references throughout the manuscript.

Comments 2: In Abstract, products should be replaced with Products.

Response 2: The word “products” in the Abstract has been corrected to “Products” as suggested. Page 1, line 9

Comments 3: In vivo and in vitro should be italicized.

Response 3: All instances of in vivo and in vitro throughout the manuscript have been italicized. Page 3, line 96; Page 6 table 2; Page 7, line 224; Page 8, line 235; Page 9, line 299,307; Page 10, lines 352,355; Page 13, line 475,478; Page 15, line 553

Comments 4: Symbols for alpha and beta should be used

Response 4: The terms “alpha” and “beta” have been replaced with the appropriate Greek symbols (α, β) throughout the manuscript. Page 9 line 320; page 17 line 629

Comments 5: Reference should be cited for figure 1

Response 5: The appropriate reference has been added to the caption of Figure 1. (Page 5, Figure1 )

Comments 6: Supplementary table should be included in main text, as there is only one table.

Response 6: The supplementary table has been moved into the main text and is now presented as Table 1 (page 4, line 167). Consequently, the original Table 1 has been renumbered as Table 2 in the manuscript (page 5 line 186)

7. Response to Comments on the Quality of English Language

No Comments on the Quality of English Language were raised by the reviewer.

8. Additional clarifications

Based on the reviewer’s comments, we have updated the manuscript with new data, which are highlighted in red throughout the text. Accordingly, the Abstract, Discussion, and References sections have also been revised to integrate these updated findings. All modifications are clearly marked in red throughout the text.

Comments 1: Abstract

By synthesizing current knowledge ....... the evolving landscape of anti-aging cosmeceuticals. ----- Aims need to place in proper position i.e., after the background.

Add conclusive statement at the end of the abstract.

Response 1: We thank the reviewer for this valuable suggestion. The aim statement has now been moved directly after the background sentences to improve clarity and logical flow. In addition, a conclusive statement has been added at the end of the abstract to summarize the key outcomes and highlight the future needs of the field.

Page 9, lines 12-14, 28-31.

Comments 2: Keywords: Avoid the words those included within the title. Arrange alphabetically.

Response 2: We revised the keywords to exclude terms already present in the title. The final keywords are arranged alphabetically, in line with journal guidelines. Page 1, lines 33-34

Comments 3: Materials and Methods:

search conducted within the past five years (2020–2025) to ensure the review reflects the
most current evidence ------ If old informative literature is available, why not considerable?

Response 3: We agree with the reviewer that some older literature remains highly informative. Accordingly, we have included selected seminal studies to ensure historical completeness and proper context. However, to comply with the journal’s requirement of reflecting current knowledge, more than half of the cited references are from the past five years (2020–2025). This balance allows the review to remain up-to-date while still acknowledging foundational contributions. Page 2, Materials and Methods paragraph

Comments 4: RESULTS:

Table 1 ----- Need to improve. AHAs/BHAs---- mentions full forms within the Table, or within the caption or within footnote. Ingredient Class--- peptides, antioxidants---- peptides are may be act as antioxidants. Therefore, restructure the ingredient class

Response 4: As suggested, Table 2 has been revised. The full forms of AHAs and BHAs are now provided in the table and footnote. The ingredient classes have been restructured, with peptides categorized by primary mechanism (signal peptides, neurotransmission-inhibiting peptides, carrier peptides), reducing overlap with antioxidants. This restructuring improves accuracy and clarity for readers. Page 6, Table 2.

Comments 5: Discussion ----- I think this section is unnecessary

Response 5: We respectfully disagree that the discussion section is unnecessary. The discussion is essential for this review because it:

1.     Synthesizes evidence across sections (mechanisms, clinical data, and regulation), highlighting converging trends and discrepancies.

2.     Critically appraises limitations of current studies, such as small clinical trial sizes and lack of standardized efficacy testing.

3.     Identifies future directions, including regulatory harmonization, personalized cosmeceuticals, microbiome-based strategies, and sustainable innovation.

Without a dedicated discussion, the manuscript would remain largely descriptive. The discussion ensures the review contributes not only a summary of existing knowledge but also a critical, forward-looking perspective valuable to both researchers and practitioners. Pages 15-17, Discussion paragraph

6. Response to Comments on the Quality of English Language

No Comments on the Quality of English Language were raised by the reviewer.

7. Additional clarifications

Based on the reviewer’s comments, we have updated the manuscript with new data, which are highlighted in red throughout the text. Accordingly, the Abstract, Discussion, and References sections have also been revised to integrate these updated findings. All modifications are clearly marked in red throughout the text.

Comments 1: It would be easier to review if line numbers were added

Response 1: Line numbers have now been added to the revised version for easier review

Comments 2: Correspondence twice

Response 2: The duplication in the Correspondence section has been corrected

Page 1, line7

Comments 3: Abstract start first sentence with capital letter

Response 3: Corrected: the abstract now begins with a capital letter.

Page 1, line 9

Comments 4: Write main findings in the abstract, not what was the aim of the review

Response 4: The abstract has been modified to emphasize the main findings rather than the aim of the review Page 1, lines 12-31

Comments 5: Objectives - space between 2 and 3

Response 5: Corrected: appropriate spacing has been added between objectives 2 and 3. Page 2, line 71

Comments 6: Latin words should be in italic (eg in vivo)

Response 6: All Latin terms (e.g., in vivo, in vitro) have been italicized throughout the manuscript. Page 3, line 96; Page 6 table 2; Page 7, line 224; Page 8, line 235; Page 9, line 299,307; Page 10, lines 352,355; Page 13, line 475,478; Page 15, line 553

Comments 7: Figure 1 - improve quality - choose better font to improve readability

Response 7: Figure 1 has been updated with higher resolution and a clearer font for improved readability. Page 5, Figure 1

Comments 8: You mention emerging research on granactive retinoid without reference. Also no reference for carrier peptides.

Response 8: A reference for hydroxypinacolone retinoate (granactive retinoid) has been added: Page 7, line 216. Additional references for carrier peptides have been added: Page 9, lines 295-308

Comments 9: Explain further why AHA induce photosensitivity

Response 9: We have expanded the section on AHAs to clarify the mechanisms underlying photosensitivity, including thinning of the stratum corneum and decreased minimal erythema dose, and cited supporting clinical studies. Page 10, lines 337-340

Comments 10: I do not see anything new in this review, majority of informations in main text of manuscript is already well known. In order to make this review acceptable for publication, in my opinion, authors should describe in depth how studies were conducted (how many participants, primary outcomes, limitations etc). I do not find appropriate claiming ingredient is effective if only one study showed positive result, please provide more data on each ingredient.

Response 10: We sincerely thank the reviewer for this valuable suggestion.

We have substantially revised the Results section to provide more detailed descriptions of study design, sample size, primary endpoints, and limitations for each major ingredient category. All changes are highlighted in red in the tracked version: Page 7. Retinoids and Retinol Derivatives paragraph, Page 8, Antioxidants paragraph, Page 9, Peptides paraghaph; Page 10, α-Hydroxy Acids and β-Hydroxy Acids

Paragraph; Page 11, Botanical Extracts paragraph

11. Response to Comments on the Quality of English Language

Point 1: Improved English throughout the manuscript

Response 11: The entire manuscript has been revised for clarity and improved scientific English.

12. Additional clarifications

Based on the reviewer’s comments, we have updated the manuscript with new data, which are highlighted in red throughout the text. Accordingly, the Abstract, Discussion, and References sections have also been revised to integrate these updated findings. All modifications are clearly marked in red throughout the text.