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Medical Diagnosis 2026
外泌体治疗皮肤光老化的机制与研究进展
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Abstract:
皮肤是人体抵御外界刺激的首要生理屏障，易受各类环境因素的影响而发生老化，其中紫外线辐射是诱发皮肤光老化的关键核心因素。皮肤光老化是紫外线致皮肤慢性退行性损伤，较自然老化更显著且累及更深，其核心发病机制包括氧化应激失衡、慢性炎症反应持续激活、细胞衰老进程加速以及细胞外基质降解异常，该病变不仅损害皮肤健康与外观形态，还可能显著增加皮肤癌的发病风险。外泌体作为细胞分泌的纳米级膜性囊泡，可携带蛋白质、核酸、脂质等多种生物活性成分，参与细胞间信号通讯并精准调控靶细胞功能。近年来外泌体已成为皮肤光老化治疗与干预领域的研究热点。本文结合近年来国内外相关研究进展，阐述皮肤光老化发病机制、外泌体生物学特性及其逆转皮肤光老化的分子机制，总结外泌体相关基础与临床研究进展，探讨其挑战与前景，为外泌体在皮肤光老化治疗中的进一步应用提供理论与实践参考。
The skin serves as the primary physiological barrier of the human body against external stimuli and is susceptible to aging under the influence of various environmental factors, among which ultraviolet (UV) radiation is the key factor inducing skin photoaging. Skin photoaging refers to chronic degenerative skin damage caused by UV radiation, which is more prominent and involves deeper skin layers compared with natural aging. Its core pathogenesis includes oxidative stress imbalance, persistent activation of chronic inflammatory responses, accelerated cellular senescence, and abnormal degradation of the extracellular matrix. This pathological change not only impairs skin health and morphological appearance but also may significantly increase the risk of skin cancer. As nanoscale membranous vesicles secreted by cells, exosomes can carry a variety of bioactive components such as proteins, nucleic acids and lipids, participate in intercellular signal communication and precisely regulate the functions of target cells. In recent years, exosomes have become a research hotspot in the field of treatment and intervention for skin photoaging. Based on the relevant research progress at home and abroad in recent years, this paper elaborates on the pathogenesis of skin photoaging, the biological characteristics of exosomes and their molecular mechanisms in reversing skin photoaging, summarizes the progress of basic and clinical research related to exosomes, and discusses the challenges and prospects of exosome application, aiming to provide theoretical and practical references for the further application of exosomes in the treatment of skin photoaging.
| [1] | Fisher, G.J., Kang, S., Varani, J., Bata-Csorgo, Z., Wan, Y., Datta, S., et al. (2002) Mechanisms of Photoaging and Chronological Skin Aging. Archives of Dermatology, 138, 1462-1470. https://doi.org/10.1001/archderm.138.11.1462 |
| [2] | Sanches Silveira, J.E.P. and Myaki Pedroso, D.M. (2014) UV Light and Skin Aging. Reviews on Environmental Health, 29, 243-254. https://doi.org/10.1515/reveh-2014-0058 |
| [3] | Tanveer, M.A., Rashid, H. and Tasduq, S.A. (2023) Molecular Basis of Skin Photoaging and Therapeutic Interventions by Plant-Derived Natural Product Ingredients: A Comprehensive Review. Heliyon, 9, e13580. https://doi.org/10.1016/j.heliyon.2023.e13580 |
| [4] | Fisher, G.J., Wang, Z., Datta, S.C., Varani, J., Kang, S. and Voorhees, J.J. (1997) Pathophysiology of Premature Skin Aging Induced by Ultraviolet Light. New England Journal of Medicine, 337, 1419-1429. https://doi.org/10.1056/nejm199711133372003 |
| [5] | Kammeyer, A. and Luiten, R.M. (2015) Oxidation Events and Skin Aging. Ageing Research Reviews, 21, 16-29. https://doi.org/10.1016/j.arr.2015.01.001 |
| [6] | Ansary, T.M., Hossain, M.R., Kamiya, K., Komine, M. and Ohtsuki, M. (2021) Inflammatory Molecules Associated with Ultraviolet Radiation-Mediated Skin Aging. International Journal of Molecular Sciences, 22, Article 3974. https://doi.org/10.3390/ijms22083974 |
| [7] | Liu, S., Meng, M., Han, S., Gao, H., Zhao, Y., Yang, Y., et al. (2021) Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes Ameliorate HaCaT Cell Photo-Aging. Rejuvenation Research, 24, 283-293. https://doi.org/10.1089/rej.2020.2313 |
| [8] | Lavasani, M., Robinson, A.R., Lu, A., Song, M., Feduska, J.M., Ahani, B., et al. (2012) Muscle-Derived Stem/Progenitor Cell Dysfunction Limits Healthspan and Lifespan in a Murine Progeria Model. Nature Communications, 3, Article No. 608. https://doi.org/10.1038/ncomms1611 |
| [9] | Kalluri, R. and LeBleu, V.S. (2020) The Biology, Function, and Biomedical Applications of Exosomes. Science, 367, eaau6977. https://doi.org/10.1126/science.aau6977 |
| [10] | Thakur, A., Shah, D., Rai, D., Parra, D.C., Pathikonda, S., Kurilova, S., et al. (2023) Therapeutic Values of Exosomes in Cosmetics, Skin Care, Tissue Regeneration, and Dermatological Diseases. Cosmetics, 10, Article 65. https://doi.org/10.3390/cosmetics10020065 |
| [11] | Raik, S., Kumar, A. and Bhattacharyya, S. (2017) Insights into Cell‐Free Therapeutic Approach: Role of Stem Cell “Soup‐Ernatant”. Biotechnology and Applied Biochemistry, 65, 104-118. https://doi.org/10.1002/bab.1561 |
| [12] | Scharffetter-Kochanek, K., Brenneisen, P., Wenk, J., Herrmann, G., Ma, W., Kuhr, L., et al. (2000) Photoaging of the Skin from Phenotype to Mechanisms. Experimental Gerontology, 35, 307-316. https://doi.org/10.1016/s0531-5565(00)00098-x |
| [13] | Braverman, I.M. and Fonferko, E. (1982) Studies in Cutaneous Aging: I. the Elastic Fiber Network. Journal of Investigative Dermatology, 78, 434-443. https://doi.org/10.1111/1523-1747.ep12507866 |
| [14] | Talwar, H.S., Griffiths, C.E.M., Fisher, G.J., Hamilton, T.A. and Voorhees, J.J. (1995) Reduced Type I and Type III Procollagens in Photodamaged Adult Human Skin. Journal of Investigative Dermatology, 105, 285-290. https://doi.org/10.1111/1523-1747.ep12318471 |
| [15] | Fisher, G.J., Talwar, H.S., Lin, J., Lin, P., McPhillips, F., Wang, Z., et al. (1998) Retinoic Acid Inhibits Induction of C-Jun Protein by Ultraviolet Radiation That Occurs Subsequent to Activation of Mitogen-Activated Protein Kinase Pathways in Human Skin in Vivo. Journal of Clinical Investigation, 101, 1432-1440. https://doi.org/10.1172/jci2153 |
| [16] | Sams, W.M. (1986) Sun-Induced Aging: Clinical and Laboratory Observations in Man. Dermatologic Clinics, 4, 509-516. https://doi.org/10.1016/s0733-8635(18)30814-3 |
| [17] | Fisher, G.J., Datta, S., Wang, Z., Li, X., Quan, T., Chung, J.H., et al. (2000) C-Jun-Dependent Inhibition of Cutaneous Procollagen Transcription Following Ultraviolet Irradiation Is Reversed by All-Trans Retinoic Acid. Journal of Clinical Investigation, 106, 663-670. https://doi.org/10.1172/jci9362 |
| [18] | Schneider, L.A., Raizner, K., Wlaschek, M., Brenneisen, P., Gethöffer, K. and Scharffetter‐Kochanek, K. (2017) UVA‐1 Exposure in Vivo Leads to an IL‐6 Surge within the Skin. Experimental Dermatology, 26, 830-832. https://doi.org/10.1111/exd.13286 |
| [19] | Johnstone, R.M., Adam, M., Hammond, J.R., Orr, L. and Turbide, C. (1987) Vesicle Formation during Reticulocyte Maturation. Association of Plasma Membrane Activities with Released Vesicles (Exosomes). Journal of Biological Chemistry, 262, 9412-9420. https://doi.org/10.1016/s0021-9258(18)48095-7 |
| [20] | Doyle, L. and Wang, M. (2019) Overview of Extracellular Vesicles, Their Origin, Composition, Purpose, and Methods for Exosome Isolation and Analysis. Cells, 8, Article 727. https://doi.org/10.3390/cells8070727 |
| [21] | Yu, B., Zhang, X. and Li, X. (2014) Exosomes Derived from Mesenchymal Stem Cells. International Journal of Molecular Sciences, 15, 4142-4157. https://doi.org/10.3390/ijms15034142 |
| [22] | Ha, D.H., Kim, S., Lee, J., Kwon, H.H., Park, G., Yang, S.H., et al. (2020) Toxicological Evaluation of Exosomes Derived from Human Adipose Tissue-Derived Mesenchymal Stem/Stromal Cells. Regulatory Toxicology and Pharmacology, 115, Article 104686. https://doi.org/10.1016/j.yrtph.2020.104686 |
| [23] | Liu, J., Chen, T., Lei, P., Tang, X. and Huang, P. (2019) Exosomes Released by Bone Marrow Mesenchymal Stem Cells Attenuate Lung Injury Induced by Intestinal Ischemia Reperfusion via the TLR4/NF-κB Pathway. International Journal of Medical Sciences, 16, 1238-1244. https://doi.org/10.7150/ijms.35369 |
| [24] | Zhou, J., Dong, Y., Liu, J., Ren, J., Wu, J. and Zhu, N. (2020) AQP5 Regulates the Proliferation and Differentiation of Epidermal Stem Cells in Skin Aging. Brazilian Journal of Medical and Biological Research, 53, e10009. https://doi.org/10.1590/1414-431x202010009 |
| [25] | Kim, S., Lee, S., Kim, H. and Kim, T. (2018) Exosomes Secreted from Induced Pluripotent Stem Cell-Derived Mesenchymal Stem Cells Accelerate Skin Cell Proliferation. International Journal of Molecular Sciences, 19, Article 3119. https://doi.org/10.3390/ijms19103119 |
| [26] | Varani, J., Warner, R.L., Gharaee-Kermani, M., Phan, S.H., Kang, S., Chung, J., et al. (2000) Vitamin a Antagonizes Decreased Cell Growth and Elevated Collagen-Degrading Matrix Metalloproteinases and Stimulates Collagen Accumulation in Naturally Aged Human Skin1. Journal of Investigative Dermatology, 114, 480-486. https://doi.org/10.1046/j.1523-1747.2000.00902.x |
| [27] | Ha, D.H., Kim, H., Lee, J., Kwon, H.H., Park, G., Yang, S.H., et al. (2020) Mesenchymal Stem/Stromal Cell-Derived Exosomes for Immunomodulatory Therapeutics and Skin Regeneration. Cells, 9, Article 1157. https://doi.org/10.3390/cells9051157 |
| [28] | Zhao, J., Li, X., Hu, J., Chen, F., Qiao, S., Sun, X., et al. (2019) Mesenchymal Stromal Cell-Derived Exosomes Attenuate Myocardial Ischaemia-Reperfusion Injury through miR-182-Regulated Macrophage Polarization. Cardiovascular Research, 115, 1205-1216. https://doi.org/10.1093/cvr/cvz040 |
| [29] | Ma, Z.J., Wang, Y.H., Li, Z.G., Wang, Y., Li, B.Y., Kang, H.Y., et al. (2019) Immunosuppressive Effect of Exosomes from Mesenchymal Stromal Cells in Defined Medium on Experimental Colitis. International Journal of Stem Cells, 12, 440-448. https://doi.org/10.15283/ijsc18139 |
| [30] | Li, K., Lin, S., Zhou, P., Guo, Y., Lin, S. and Ji, C. (2025) The Role of Exosomal LncRNAs in Mediating Apoptosis and Inflammation in UV-Induced Skin Photoaging. Frontiers in Cell and Developmental Biology, 13, Article ID: 1538197. https://doi.org/10.3389/fcell.2025.1538197 |
| [31] | Labunskyy, V.M. and Gladyshev, V.N. (2013) Role of Reactive Oxygen Species-Mediated Signaling in Aging. Antioxidants & Redox Signaling, 19, 1362-1372. https://doi.org/10.1089/ars.2012.4891 |
| [32] | Zhang, M., Wang, L., Huang, S. and He, X. (2021) Exosomes with High Level of miR-181c from Bone Marrow-Derived Mesenchymal Stem Cells Inhibit Inflammation and Apoptosis to Alleviate Spinal Cord Injury. Journal of Molecular Histology, 52, 301-311. https://doi.org/10.1007/s10735-020-09950-0 |
| [33] | Zhang, H., Xiao, X., Wang, L., Shi, X., Fu, N., Wang, S., et al. (2024) Human Adipose and Umbilical Cord Mesenchymal Stem Cell-Derived Extracellular Vesicles Mitigate Photoaging via TIMP1/Notch1. Signal Transduction and Targeted Therapy, 9, Article No. 294. https://doi.org/10.1038/s41392-024-01993-z |
| [34] | 孙艳, 赵红艺, 丁金萍, 杨洋. 来源不同外泌体抗皮肤衰老的研究进展[J]. 中华医学美学美容杂志, 2024, 30(2): 191-195. |
| [35] | Quan, T., Qin, Z., Xia, W., Shao, Y., Voorhees, J.J. and Fisher, G.J. (2009) Matrix-Degrading Metalloproteinases in Photoaging. Journal of Investigative Dermatology Symposium Proceedings, 14, 20-24. https://doi.org/10.1038/jidsymp.2009.8 |
| [36] | Hajialiasgary Najafabadi, A., Soheilifar, M.H. and Masoudi-Khoram, N. (2024) Exosomes in Skin Photoaging: Biological Functions and Therapeutic Opportunity. Cell Communication and Signaling, 22, Article No. 38. https://doi.org/10.1186/s12964-023-01451-3 |
| [37] | Gao, W., Wang, X., Si, Y., Pang, J., Liu, H., Li, S., et al. (2021) Exosome Derived from ADSCs Attenuates Ultraviolet B‐mediated Photoaging in Human Dermal Fibroblasts. Photochemistry and Photobiology, 97, 795-804. https://doi.org/10.1111/php.13370 |
| [38] | Chen, J., Li, P., Zhang, T., Xu, Z., Huang, X., Wang, R., et al. (2022) Review on Strategies and Technologies for Exosome Isolation and Purification. Frontiers in Bioengineering and Biotechnology, 9, Article ID: 811971. https://doi.org/10.3389/fbioe.2021.811971 |
| [39] | Wang, C., Tsai, T. and Lee, C. (2024) Regulation of Exosomes as Biologic Medicines: Regulatory Challenges Faced in Exosome Development and Manufacturing Processes. Clinical and Translational Science, 17, e13904. https://doi.org/10.1111/cts.13904 |
| [40] | 文武龙, 张炜烨, 孙鑫, 梁霄, 杨婧, 王锐. 结合外泌体的微针经皮给药系统研究进展[J]. 中国药房, 2024, 35(13): 1663-1667 |
| [41] | Jeyaram, A. and Jay, S.M. (2017) Preservation and Storage Stability of Extracellular Vesicles for Therapeutic Applications. The AAPS Journal, 20, Article No. 1. https://doi.org/10.1208/s12248-017-0160-y |
| [42] | Verma, N. and Arora, S. (2025) Navigating the Global Regulatory Landscape for Exosome-Based Therapeutics: Challenges, Strategies, and Future Directions. Pharmaceutics, 17, Article 990. https://doi.org/10.3390/pharmaceutics17080990 |
| [43] | 娄东晓, 付清玲. 间充质干细胞来源小细胞外囊泡的临床研究现状[J]. 中国研究型医院(中英文), 2025, 12(3): 33-40. |
| [44] | Xu, G., Jin, J., Fu, Z., Wang, G., Lei, X., Xu, J., et al. (2025) Extracellular Vesicle-Based Drug Overview: Research Landscape, Quality Control and Nonclinical Evaluation Strategies. Signal Transduction and Targeted Therapy, 10, Article No. 255. https://doi.org/10.1038/s41392-025-02312-w |
| [45] | Bai, G., Truong, T.M., Pathak, G.N., Benoit, L. and Rao, B. (2024) Clinical Applications of Exosomes in Cosmetic Dermatology. Skin Health and Disease, 4, Article No. 348. https://doi.org/10.1002/ski2.348 |
