Metformin-Engineered Extracellular Vesicles: Strategic Role in Aging Skin Repair

Schematic diagram shows the Met-EV–mediated biological performance.
Met-EV could mediate the activation of mitophagy, rescue of mitochondria, and reprogramming of energy metabolism in fibroblasts.
Researchers from the Shanghai Jiao Tong University School of Medicine have discovered a novel approach to enhancing the repair of aging skin, a common issue marked by impaired wound healing and cellular senescence. The study, which involved both patient samples and mouse models, highlights the potential of metabolic regulation in accumulated senescent cells (SnCs) for maintaining tissue homeostasis and promoting effective tissue repair.

The research identified significant energy metabolic alterations in the aging skin of both humans and mice. These changes underscore the critical role of ATP metabolism in cell activation and tissue repair in aged individuals. The study demonstrated that Metformin-Engineered Extracellular Vesicles (Met-EV) could significantly enhance skin repair in aged mice. This was achieved by ameliorating cellular senescence and restoring cellular functions. Treatment with Met-EV led to a remodeling of ATP metabolism, characterized by reduced glycolysis and enhanced oxidative phosphorylation (OXPHOS).

Met-EV treatment also rescued mitochondria dysfunctions and mitigated mitophagy suppressions induced by senescence. This indicates a crucial role for Met-EV in remodeling mitochondrial functions through mitophagy, ensuring adequate ATP production for aged tissue repair.

The findings of this study reveal the underlying mechanism of SnCs rejuvenation by extracellular vesicles (EVs) and position disturbed energy metabolism as a pivotal therapeutic target for addressing age-related defects.

Read the full paper.

Join Skin Ageing & Challenges on November 5-6, 2024 at Corinthia Palace Malta to know more about extracellular vesicles’ role in skin aging and wound healing. 

Photo credits: Yu Zhuang et al., Energy metabolism as therapeutic target for aged wound repair by engineered extracellular vesicle. Sci. Adv. 10, eadl0372 (2024).

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