Li Yuping,1,7,* Linlin Guan,2 Isabelle Becher,3 Kira S. Makarova,4 Xueli Cao,2 Surabhi Hareendranath,1 Jingwen Guan,1 Frank Stein,3 Siqi Yang,2 Arne Boergel,3 Karine Lapouge,3 Kim Remans,3 David Agard,5 Mikhail Savitski,3 Athanasios Typas,3 Eugene V. Koonin,4 Yue Feng,2,* and Joseph Bondy-Denomy1,6,8,*

1 Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94403, USA

2 State Key Laboratory of Green Biomanufacturing, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China

3 European Molecular Biology Laboratory (EMBL), Meyerhofstraße 1, 69117 Heidelberg, Germany

4 Computational Biology Branch, Division of Intramural Research, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA

5 The Chan-Zuckerberg Institute for Advanced Biological Imaging and the Department of Biochemistry, University of California, San Francisco, San Francisco, CA 94143, USA

6 Quantitative Biosciences Institute, University of California, San Francisco, San Francisco, CA 94403, USA

7 Present address: Biozentrum, University of Basel, Basel 4056, Switzerland

8 Lead contact

*Correspondence: 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (L.Y.), 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (Y.F.), 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (J.B.-D.)

https://doi.org/10.1016/j.cell.2025.02.016

SUMMARY

Jumbo bacteriophages of the fKZ-like family assemble a lipid-based early phage infection (EPI) vesicle and a proteinaceous nucleus-like structure during infection. These structures protect the phage from nucleases and may create selective pressure for immunity mechanisms targeting this specific phage family. Here, we identify ‘‘jumbo phage killer’’ (Juk), a two-component immune system that terminates infection of fKZ-like phages, suppressing the expression of early phage genes and preventing phage DNA replication and phage nucleus assembly while saving the cell. JukA (formerly YaaW) rapidly senses the EPI vesicle by binding to an early-expressed phage protein, gp241, and then directly recruits JukB. The JukB effector structurally resembles a pore-forming toxin and destabilizes the EPI vesicle. Functional anti-fKZ JukA homologs are found across bacterial phyla, associated with diverse effectors. These findings reveal a widespread defense system that specifically targets early events executed by fKZ-like jumbo phages prior to phage nucleus assembly.

Li Yuping,1,7,* Linlin Guan,2 Isabelle Becher,3 Kira S. Makarova,4 Xueli Cao,2 Surabhi Hareendranath,1 Jingwen Guan,1 Frank Stein,3 Siqi Yang,2 Arne Boergel,3 Karine Lapouge,3 Kim Remans,3 David Agard,5 Mikhail Savitski,3 Athanasios Typas,3 Eugene V. Koonin,4 Yue Feng,2,* and Joseph Bondy-Denomy1,6,8,*

1 Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94403, USA

2 State Key Laboratory of Green Biomanufacturing, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China

3 European Molecular Biology Laboratory (EMBL), Meyerhofstraße 1, 69117 Heidelberg, Germany

4 Computational Biology Branch, Division of Intramural Research, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA

5 The Chan-Zuckerberg Institute for Advanced Biological Imaging and the Department of Biochemistry, University of California, San Francisco, San Francisco, CA 94143, USA

6 Quantitative Biosciences Institute, University of California, San Francisco, San Francisco, CA 94403, USA

7 Present address: Biozentrum, University of Basel, Basel 4056, Switzerland

8 Lead contact

*Correspondence: 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (L.Y.), 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (Y.F.), 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (J.B.-D.)

https://doi.org/10.1016/j.cell.2025.02.016

SUMMARY

Jumbo bacteriophages of the fKZ-like family assemble a lipid-based early phage infection (EPI) vesicle and a proteinaceous nucleus-like structure during infection. These structures protect the phage from nucleases and may create selective pressure for immunity mechanisms targeting this specific phage family. Here, we identify ‘‘jumbo phage killer’’ (Juk), a two-component immune system that terminates infection of fKZ-like phages, suppressing the expression of early phage genes and preventing phage DNA replication and phage nucleus assembly while saving the cell. JukA (formerly YaaW) rapidly senses the EPI vesicle by binding to an early-expressed phage protein, gp241, and then directly recruits JukB. The JukB effector structurally resembles a pore-forming toxin and destabilizes the EPI vesicle. Functional anti-fKZ JukA homologs are found across bacterial phyla, associated with diverse effectors. These findings reveal a widespread defense system that specifically targets early events executed by fKZ-like jumbo phages prior to phage nucleus assembly.

Sven Klumpe,1,9,* Kirsten A. Senti,2 Florian Beck,1 Jenny Sachweh,3 Bernhard Hampoelz,3 Paolo Ronchi,4 Viola Oorschot,4 Marlene Brandstetter,6 Assa Yeroslaviz,5 John A.G. Briggs,7 Julius Brennecke,2,* Martin Beck,3,8,* and Ju¨ rgen M. Plitzko1,*

1 Research Group CryoEM Technology, Max Planck Institute of Biochemistry, Martinsried, Germany

2 Institute of Molecular Biotechnology Austria (IMBA), Vienna, Austria

3 Department Molecular Sociology, Max Planck Institute of Biophysics, Frankfurt, Germany

4 EMBL EM Core Facility, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany

5 Computational Systems Biochemistry, Bioinformatics Core Facility, Max Planck Institute of Biochemistry, Martinsried, Germany

6 Electron Microscopy Facility, Vienna BioCenter Core Facilities, Vienna, Austria

7 Department of Cell and Virus Structure, Max Planck Institute of Biochemistry, Martinsried, Germany

8 Institute of Biochemistry, Goethe University Frankfurt, Frankfurt, Germany

9 Lead contact

*Correspondence: 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (S.K.), 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (J.B.), 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (M.B.), 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (J.M.P.)

https://doi.org/10.1016/j.cell.2025.02.003

SUMMARY

Long terminal repeat (LTR) retrotransposons belong to the transposable elements (TEs), autonomously replicating genetic elements that integrate into the host,s genome. Among animals, Drosophila melanogaster serves as an important model organism for TE research and contains several LTR retrotransposons, including the Ty1-copia family, which is evolutionarily related to retroviruses and forms viruslike particles (VLPs). In this study, we use cryo-focused ion beam (FIB) milling and lift-out approaches to visualize copia VLPs in ovarian cells and intact egg chambers, resolving the in situ copia capsid structure to 7.7 A˚ resolution by cryoelectron tomography (cryo-ET). Although cytoplasmic copia VLPs vary in size, nuclear VLPs are homogeneous and form densely packed clusters, supporting a model in which nuclear import acts as a size selector. Analyzing flies deficient in the TE-suppressing PIWI-interacting RNA (piRNA) pathway, we observe copia,s translocation into the nucleus during spermatogenesis. Our findings provide insights into the replication cycle and cellular structural biology of an active LTR  retrotransposon.

Suradwadee Thungmungmee1 , Boonchoo Sritularak2 , Nakuntwalai Wisidsri1 , Nattakan Kanana3 , Nattika Nimmano3

1 Faculty of Integrative Medicine, Rajamangala University of Technology Thanyaburi, Pathum Thani, Thailand;

2 Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Science, Chulalongkorn University, Bangkok, Thailand;

3 Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand

Correspondence: Nattika Nimmano, Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand, Tel +66 0 2188399, Fax +66 0 2188401, Email 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。

Purpose: The study aimed to investigate in vitro anti-aging activities of 29 Dendrobium spp. and develop and characterize microemulsions (MEs) for topical application.

Methods: Antioxidant activity was determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH), H2O2 scavenging, and ferric reducing antioxidant power (FRAP) assays. The anti-collagenase (MMP-1 and MMP-2) and anti-elastase activities were also evaluated.

Cytotoxicity and human intracellular reactive oxygen species (ROS) levels were determined using resazurin reduction and 2′,7′- dichlorofluorescin diacetate (DCFDA) assays, respectively. D. kentrophyllum extract-loaded microemulsion (DKME) was then prepared and optimized. The stability of DKME was studied using a heating-cooling cycle.

Results: D. kentrophyllum appeared to be the best candidate anti-aging agent because of its antioxidant, anti-collagenase, and antielastase activities. The extract was safe for human skin cells at a concentration of 6.25–100 μg/mL. It also decreased the intracellular ROS-induced ultraviolet B (UVB) irradiation compared to that in the control. DKME comprising Tween 80:ethanol (5:1), water, and isononyl isononanoate showed a suitable appearance, droplet size, polydisperse index, zeta potential, pH, and viscosity. This formulation demonstrated desirable physical and chemical stability, with non-cytotoxic effects.

Conclusion: DKME is considered a promising anti-aging product. However, an in vivo study of this optimized formulation might be evaluated in further study for anti-aging purposes.

Keywords: reactive oxygen species, anti-aging activities, Dendrobium kentrophyllum, microemulsion

Federica Li Pomi 1 , Andrea d’Aloja 2 , Dario Valguarnera 2 , Mario Vaccaro 2 and Francesco Borgia 2,*

1 Department of Precision Medicine in Medical, Surgical and Critical Care (Me.Pre.C.C.), University of Palermo, 90127 Palermo, Italy; 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。

2 Department of Clinical and Experimental Medicine, Section of Dermatology, University of Messina, 98125 Messina, Italy; 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (A.d.); 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (D.V.); 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (M.V.) * Correspondence: 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。

Academic Editor: Vita Lesauskaite.

Received: 3 January 2025

Revised: 14 January 2025

Accepted: 22 January 2025

Published: 24 January 2025

Citation: Li Pomi, F.; d’Aloja, A.;

Valguarnera, D.; Vaccaro, M.; Borgia, F.

Exploring Anti–Aging Effects of Topical Treatments for Actinic Keratosis. Medicina 2025, 61, 207.

https://doi.org/10.3390/ medicina61020207

Copyright: © 2025 by the authors.

Published by MDPI on behalf of the Lithuanian University of Health Sciences. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license

(https://creativecommons.org/ licenses/by/4.0/)

Abstract: Background and Objectives: Actinic keratosis (AK) is a precancerous cutaneous lesion driven by chronic ultraviolet (UV) exposure, often coexisting with features of photoaging, such as wrinkles and pigmentary irregularities. Recent evidence suggests that treatments for AK may also counteract photoaging through shared molecular pathways, including oxidative stress and inflammation. This narrative review explores the dual benefits of AK therapies, highlighting their potential anti-aging and skin-lightening effects, and implications for improving skin appearance alongside lesion clearance. Materials and Methods: The literature was analyzed to assess the efficacy, mechanisms, and cosmetic outcomes of commonly used AK treatments, including topical agents (5-fluorouracil (5-FU), imiquimod, diclofenac, and tirbanibulin), and photodynamic therapy (PDT). Studies highlighting their effects on photoaged skin, collagen remodeling, pigmentation, and patient satisfaction were reviewed. Results: PDT emerged as the most validated treatment, demonstrating improved collagen synthesis, skin texture, and pigmentation. 5-FU showed remodeling of the dermal matrix and increased procollagen levels, but local skin reactions represent a major limitation. Imiquimod enhanced dermal fibroplasia and reduced solar elastosis, while diclofenac provided mild photodamage improvements with minimal adverse effects. Tirbanibulin showed promising aesthetic outcomes, including skin lightening and a reduction in mottled pigmentation, with favorable tolerability. Conclusions: AK therapies offer a dual-purpose strategy, addressing both precancerous lesions and cosmetic concerns associated with photoaging. While PDT remains the gold standard, emerging agents like tirbanibulin ointment exhibit substantial potential. Future research should focus on optimizing treatment protocols and evaluating long-term cosmetic outcomes to enhance patient satisfaction and compliance.

Keywords: actinic keratosis; anti–aging; oxidative stress; photodynamic therapy; skin aging; skin lightening; solar lentigo; tirbanibulin; 5–fluorouracil

Chidchanok Prathumwon a , Songyot Anuchapreeda b , Kanokwan Kiattisin a , Pawaret Panyajai b , Panikchar Wichayapreechar d , Young-Joon Surh e , Chadarat Ampasavate a,c,*

a Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand

b Division of Clinical Microscopy, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand

c Center for Excellence in Pharmaceutical Nanotechnology, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand

d Department of Cosmetic Sciences, School of Pharmaceutical Sciences, University of Phayao, Phayao 56000, Thailand

e College of Pharmacy, Seoul National University, Seoul 151-741, South Korea

Corresponding author at: Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand.

E-mail address: 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (C. Ampasavate).

ABSTRACT

Curcumin (Cur) and epigallocatechin gallate (EGCG), the primary active compounds in turmeric and green tea, respectively, have been investigated for their anti-aging potential. The Cur and EGCG combination was encapsulated in sustained-release nanostructured lipid carriers (NLCs) to enhance their bioactivities and pharmaceutical properties. A significant enhancement in the antioxidant activities of the Cur and EGCG combination was observed at an optimal ratio, as demonstrated by the 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay (118.83 ± 3.78 %), ferric ion reducing antioxidant power assay (217.25 ± 13.45 %), and lipid peroxidation inhibition assay (106.08 ± 12.93 %), compared to Cur alone without compromising the antioxidant activities and total phenolic content of EGCG. This is due to the enhancement of total phenolic content of the combination of 218.83 ± 10.57 %. For anti-aging activities, the combination exhibited stimulation of SIRT1 protein and inhibition of collagenase and elastase of 27.53 ± 0.73 %, 43.70 ± 1.05 % and 51.76 ± 6.52 % compared with that achieved with Cur alone, respectively. The incorporation of the Cur and EGCG combination into NLCs resulted in high entrapment efficiencies of 98.60 ± 0.05 % for Cur and 98.40 ± 0.08 % for EGCG, with corresponding loading capacities of 0.789 ± 0.001 % and 3.935 ± 0.003 %, respectively. When formulated NLCs into an emulgel base, the system demonstrated sustained release profiles over 48 h, with 12.82 ± 0.99 % release of Cur and 63.77 ± 5.76 % release of EGCG. Significant skin retention was also observed after 24 h, with 23.88 ± 1.71 % Cur and 22.79 ± 4.65 % EGCG retained in the skin. Therefore, Cur: EGCG-loaded NLCs in emulgel can deliver the active compounds into the dermis, enhancing skin penetration, sustained delivery, and anti-aging activity superior to each conventional single active compound in topical formulations.

ARTICLE INFO

Keywords: Curcumin   Epigallocatechin gallate    SIRT1  Anti-aging  HaCaT cells  Nanostructured lipid carriers  Skin

Nahid Amini | Christina Osterlund | Jessen Curpen | Virginie Lafon-Kolb | Thibaud Richard | Lene Visdal-Johnsen Global Research and Development, Oriflame Cosmetics, Stockholm, Sweden

Correspondence: Nahid Amini (该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。)

Received: 19 September 2024 | Revised: 15 November 2024 | Accepted: 25 November 2024

Funding: The authors received no specific funding for this work.

Keywords: collagen | data mining | dermal density | Glycyrrhiza uralensis | phytoestrogen

ABSTRACT

Background: The dermal extracellular matrix (ECM) is a dynamic scaffold composed mainly of proteins, with collagen as the key structural component providing resilience and support to the skin. Post-menopause, declining estrogen levels lead to a significant reduction in skin health, notably a 30% decrease in collagen types I and III within 5 years.

Aim: To discover natural extracts that stimulate collagen production.

Methods: We utilized PathwayStudio to analyze protein–protein interactions and identify regulators of essential collagen types. Our study assessed Glycyrrhiza uralensis extract's ability to boost collagen production and enhance dermal density both in vitro and in vivo.

Results: PathwayStudio analysis highlighted phytoestrogens including glycyrrhizin, isoliquiritigenin, liquiritigenin, liquiritin, and glabrol, as potential candidates. Liquorice rhizome (G. uralensis), used in traditional Chinese medicine, is rich in phytoestrogens like liquiritigenin. The G. uralensis extract increased collagen I and III gene expression and pro-collagen I protein levels in human dermal fibroblasts and inhibited UVB and pollution-induced matrix metalloproteinase-1 (MMP1) production. In an in vivo study, a topical formulation containing the extract significantly improved dermal density after 56days, measured by the DUB SkinScanner.

Conclusions: These findings suggest G. uralensis extract as a promising agent for enhancing collagen production and skin health, particularly in postmenopausal women. Further research is needed to explore its mechanisms and long-term effects.

Trung Quang Nguyen 1 , Thinh Van Pham 2 , Yusuf Andriana 3 and Minh Ngoc Truong 4,5,*

1 Institute of Environmental Science and Public Health, 18 Hoang Quoc Viet Street, Cau Giay, Hanoi 11353, Vietnam; 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。

2 Faculty of Tourism and Culinary, Ho Chi Minh City University of Industry and Trade, Ho Chi Minh City 70000, Vietnam; 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。

3 Research Center for Appropriate Technology, Indonesian Institute of Sciences, Subang 41213, Indonesia; 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。

4 Center for High Technology Research and Development, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet Street, Cau Giay, Hanoi 100000, Vietnam

5 Graduate University of Science and Technology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet Street, Cau Giay, Hanoi 100000, Vietnam

* Correspondence: 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。

Academic Editor: Shige Wang

Received: 9 December 2024

Revised: 23 December 2024

Accepted: 25 December 2024

Published: 3 January 2025

Citation: Nguyen, T.Q.; Van Pham, T.; Andriana, Y.; Truong, M.N. Cordyceps militaris-Derived Bioactive Gels:

Therapeutic and Anti-Aging Applications in Dermatology. Gels 2025, 11, 33. https://doi.org/ 10.3390/gels11010033

Copyright: © 2025 by the authors.

Licensee MDPI, Basel, Switzerland.

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/ licenses/by/4.0/).

Abstract: Cordyceps militaris is a medicinal mushroom widely utilized in traditional East Asian medicine, recognized for its diverse therapeutic properties. This review explores the potential of C. militaris-derived bioactive gels for applications in dermatology and skincare, with a particular focus on their therapeutic and anti-aging benefits. In response to the rising incidence of skin cancers and the growing demand for natural bioactive ingredients, C. militaris has emerged as a valuable source of functional compounds, including cordycepin, polysaccharides, and adenosine. These compounds exhibit multiple bioactivities, including apoptosis induction, cell cycle arrest, and anti-inflammatory effects, which have been shown to be particularly effective against melanoma and other skin cancers. Additionally, the antioxidant properties of C. militaris enhance skin resilience by scavenging reactive oxygen species, reducing oxidative stress, and promoting collagen synthesis, thereby addressing skin health and anti-aging requirements. The potential for incorporating C. militaris compounds into gel-based formulations for skincare is also ex amined, either as standalone bioactives or in combination with synergistic ingredients. Emphasis is placed on the necessity of clinical trials and standardization to establish the safety, efficacy, and reproducibility of such applications. By providing a safer alternative to synthetic agents, C. militaris-derived bioactive gels represent a promising advancement in dermatology and skincare.

Keywords: anti-aging; bioactive compounds; Cordyceps militaris; dermatology; skincare; therapeutic properties

Andrada Pintea 1 , Andrei Manea 1,* , Cezara Pintea 1 , Robert-Alexandru Vlad 2 , Magdalena Bîrsan 3 , Paula Antonoaea 2 , Emöke Margit Rédai 2 and Adriana Ciurba 2

1 Medicine and Pharmacy Doctoral School, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Targu Mures, Romania

2 Pharmaceutical Technology and Cosmetology Department, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540142 Targu Mures, Romania; 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (A.C.)

3 Department of Drug Industry and Pharmaceutical Biotechnology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania

* Correspondence: 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。

Academic Editors: Maurice Am Van

Steensel and Jean-Luc Poyet

Received: 29 November 2024

Revised: 28 December 2024

Accepted: 8 January 2025

Published: 9 January 2025

Citation: Pintea, A.; Manea, A.; Pintea, C.; Vlad, R.-A.; Bîrsan, M.; Antonoaea, P.; Rédai, E.M.; Ciurba, A.

Peptides: Emerging Candidates for the Prevention and Treatment of Skin

Senescence: A Review. Biomolecules 2025, 15, 88. https://doi.org/ 10.3390/biom15010088

Copyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland.

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/ licenses/by/4.0/).

Abstract: One class of cosmetic compounds that have raised interest of many experts is peptides. The search for ingredients with good biocompatibility and bioactivity has led to the use of peptides in cosmetic products. Peptides are novel active ingredients that improve collagen synthesis, enhance skin cell proliferation, or decrease inflammation. Based on their mechanism of action, they can be classified into signal peptides, carrier peptides, neurotransmitter inhibitor peptides, and enzyme inhibitor peptides. This review focuses on the main types of peptides and their application in the cosmetic field, underlining their main limitations. One of the most significant drawbacks of cosmetic peptides is their poor permeability through membranes, which limits their delivery and effectiveness. As a result, this review follows the methods used for improving permeability through the stratum corneum. Increasing peptide bioavailability and stability for enhanced delivery to the desired site of action and visible effects have become central points for the latest research due to their promising features. For this purpose, several methods have been identified and described. Physical techniques include thermal ablation (radiofrequency and laser), electrical methods (electroporation, iontophoresis), mechanical approach (microneedles), and ultrasounds. As an alternative, innovative formulations have been developed in nanosystems such as liposomes, niosomes, ethosomes, nanoemulsions, and other nanomaterials to reduce skin irritation and improve product effectiveness. The purpose of this review is to provide the latest information regarding these noteworthy molecules and the reasoning behind their use in cosmetic formulations.

Keywords: cosmetic peptides; anti-aging products; permeability; nano-systems

Yajing Li , Lan Xiang and Jianhua Qi *

College of Pharmaceutical Sciences, Zhejiang University, Yu Hang Tang Road 866, Hangzhou 310058, China; 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (Y.L.); 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (L.X.)

* Correspondence: 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。

Academic Editors: Marina Garcia-Macia and Álvaro F. Fernández

Received: 18 February 2025

Revised: 5 March 2025

Accepted: 5 March 2025

Published: 7 March 2025

Citation: Li, Y.; Xiang, L.; Qi, J. Procyanidin A1 from Peanut Skin Exerts Anti-Aging Effects and Attenuates Senescence via Antioxidative Stress and Autophagy Induction. Antioxidants 2025, 14, 322.

https://doi.org/10.3390/ antiox14030322

Copyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland.

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license

(https://creativecommons.org/ licenses/by/4.0/)

Abstract: The aging population is steadily increasing, with aging and age-related diseases serving as major risk factors for morbidity, mortality, and economic burden. Peanuts, known as the “longevity nut” in China, have been shown to offer various health benefits, with peanut skin extract (PSE) emerging as a key compound of interest. This study investigates the bioactive compound in PSE with anti-aging potential and explores its underlying mechanisms of action. Procyanidin A1 (PC A1) was isolated from PSE, guided by the K6001 yeast replicative lifespan model. PC A1 prolonged the replicative lifespan of yeast and the yeast-like chronological lifespan of PC12 cells. To further confirm its anti-aging effect, cellular senescence, a hallmark of aging, was assessed. In senescent cells induced by etoposide (Etop), PC A1 alleviated senescence by reducing ROS levels, decreasing the percentage of senescent cells, and restoring proliferative capacity. Transcriptomics analysis revealed that PC A1 induced apoptosis, reduced senescence-associated secretory phenotype (SASP) factors, and modulated the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. The antioxidative capacity of PC A1 was also evaluated, showing enhanced resistance to oxidative stress in PC12 cells by reducing reactive oxygen species (ROS) and malondialdehyde (MDA) levels and increasing superoxide dismutase (SOD) activity. Moreover, PC A1 induced autophagy, as evidenced by an increase in fluorescence-labeled autophagic compartments and confirmation via Western blot analysis of autophagy-related proteins. In addition, the treatment of an autophagy inhibitor abolished the antioxidative stress and senescence-alleviating effects of PC A1. These findings reveal that PC A1 extended lifespans and alleviated cellular senescence by enhancing oxidative stress resistance and inducing autophagy, positioning it as a promising candidate for further exploration as a geroprotective agent.

Keywords: aging; peanut skin; procyanidin A1; cell senescence; antioxidative stress; autophagy; PI3K/Akt signaling pathway