Exosome-Mediated Rewiring of Oxidative Stress–Inflammation–ECM Remodeling Axis Mitigates UVB-Triggered Skin Photoaging

Fang Yu,1– 4,* Jingfeng Zhou,2– 4,* Min Chen,1 Yi Liu,5 Jing Qiu,6 Junhao Chen,7 Yuanyin Teng,8 Keyi Gou,2– 4 Yuan Tang,2– 4 Yizheng Xu,9 Zhu Wu,10 Zhongsong Zhang,2– 4 Long Chen2– 4 1Department of Dermatology, Nanbu People’s Hospital, Nanchong, Sichuan Province, 637300, People’s Republic of China; 2The Second Affiliated Hospital of Chengdu Medical College, Nuclear Industry 416 Hospital, Chengdu, Sichuan Province, 610000, People’s Republic of China; 3Non-Coding RNA and Drug Discovery Key Laboratory of Sichuan Province, School of Basic Medical Sciences, Chengdu Medical College, Chengdu, Sichuan, 610550, People’s Republic of China; 4School of Basic Medical Sciences, Chengdu Medical College, Chengdu, 610550, People’s Republic of China; 5Pidu District People’s Hospital and The Third Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan Province, 611700, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Chengdu Medical College, Chengdu Medical College, Chengdu, Sichuan Province, 610550, People’s Republic of China; 7Department of Urology, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, 650032, People’s Republic of China; 8Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang Province, 310003, People’s Republic of China; 9Department of Radiology, The People’s Hospital of Yanjiang District, Ziyang, Sichuan Province, 641300, People’s Republic of China; 10The Hunan Provincial Key Laboratory of the TCM Agricultural Biogenomics, Changsha Medical University, Changsha, 410219, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhongsong Zhang; Long Chen, Email [email protected]; [email protected]: Photoaging is a chronic and multifactorial form of skin aging primarily induced by ultraviolet (UV) radiation. It is characterized by oxidative stress, DNA damage, chronic inflammation, pigmentary alterations, and extracellular matrix (ECM) degradation, which ultimately lead to wrinkle formation, loss of elasticity, and uneven pigmentation. Exosomes, nanosized extracellular vesicles that mediate intercellular communication, have attracted growing attention in photoaging research. Emerging evidence suggests that exosomes may both contribute to photoaging and promote tissue repair by modulating cellular responses. However, despite the growing body of evidence, the field still lacks an integrated review that links exosome biogenesis and functional properties to the mechanisms of photoaging, their therapeutic potential, and the major translational barriers to clinical application. Therefore, this review aims to systematically summarize the biogenesis and biological properties of exosomes, clarify their mechanistic roles in photoaging, particularly in the regulation of oxidative stress, and evaluate their potential as therapeutic agents and delivery platforms for anti-photoaging and regenerative medicine. It further examines the effects of native exosomes derived from multiple cell sources, with a focus on stem cells, keratinocytes, and melanocytes. Finally, it outlines translational opportunities for exosome-based interventions in anti-photoaging and regenerative medicine, including engineered exosome mimetics and other nanomedicine-based strategies. It also highlights the key knowledge gaps and technical challenges that must be addressed to facilitate clinical translation. In conclusion, exosomes represent a promising yet still evolving strategy for the prevention and treatment of photoaging because of their dual roles in intercellular signaling and tissue regeneration. Nevertheless, further standardization of isolation, characterization, engineering, safety assessment, and regulatory evaluation is essential before their full clinical potential can be realized.Keywords: exosomes, photoaging, UVB, oxidative stress, regenerative medicine, nanomedicine