2. Academic Validation
  3. Energy metabolism as therapeutic target for aged wound repair by engineered extracellular vesicle

Energy metabolism as therapeutic target for aged wound repair by engineered extracellular vesicle

  • Sci Adv. 2024 Apr 12;10(15):eadl0372. doi: 10.1126/sciadv.adl0372.
Yu Zhuang 1,  Shengjie Jiang 1,  Xiaoling Deng 1,  An Lao 1,  Xiaolin Hua 2,  Yun Xie 3,  Lingyong Jiang 1,  Xudong Wang 1,  Kaili Lin 1
Affiliations

Affiliations

  • 1 Department of Oral and Cranio-maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology; Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai, China.
  • 2 Obstetrics Department, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.
  • 3 Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
PMID: 38608014 DOI: 10.1126/sciadv.adl0372
Abstract

Aging skin, vulnerable to age-related defects, is poor in wound repair. Metabolic regulation in accumulated senescent cells (SnCs) with aging is essential for tissue homeostasis, and adequate ATP is important in cell activation for aged tissue repair. Strategies for ATP metabolism intervention hold prospects for therapeutic advances. Here, we found energy metabolic changes in aging skin from patients and mice. Our data show that metformin engineered EV (Met-EV) can enhance aged mouse skin repair, as well as ameliorate cellular senescence and restore cell dysfunctions. Notably, ATP metabolism was remodeled as reduced glycolysis and enhanced OXPHOS after Met-EV treatment. We show Met-EV rescue senescence-induced mitochondria dysfunctions and Mitophagy suppressions, indicating the role of Met-EV in remodeling mitochondrial functions via Mitophagy for adequate ATP production in aged tissue repair. Our results reveal the mechanism for SnCs rejuvenation by EV and suggest the disturbed energy metabolism, essential in age-related defects, to be a potential therapeutic target for facilitating aged tissue repair.

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