An energy metabolism-engaged nanomedicine maintains mitochondrial homeostasis to alleviate cellular ageing.

Liyuan Chen, Yijie Fan, Nan Jiang, Xiaoshuai Huang, Min Yu, He Zhang, Zhengren Xu, Danqing He, Yu Wang, Chengye Ding, Xiaolan Wu, Chang Li, Shiying Zhang, Hangbo Liu, Xinmeng Shi, Fanghui Zhang, Ting Zhang, Dan Luo, Cunyu Wang, Yan Liu

Department of Orthodontics, National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing Key Laboratory of Digital Stomatology, Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health, NMPA Key Laboratory for Dental Materials, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Peking University School and Hospital of Stomatology, Beijing, People's Republic of China.Department of Orthodontics, National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing Key Laboratory of Digital Stomatology, Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health, NMPA Key Laboratory for Dental Materials, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Peking University School and Hospital of Stomatology, Beijing, People's Republic of China. · pubmed

Paper

Abstract

Energy restriction is closely related to cellular senescence and species longevity. Here, based on the structure and function of ATP synthase, a key enzyme for energy generation, we develop energy metabolism-engaged nanomedicines (EM-eNMs) to rejuvenate aged stromal/stem cells, and help to prevent skeletal ageing. We show that EM-eNMs infiltrate the mitochondria of aged bone marrow mesenchymal stromal/stem cells (BMMSCs), driving mitochondrial fission, mitophagy, glycolysis and maintaining BMMSC stemness and multifunction. The EM-eNMs directly bind to the ATP synthase and promote mitophagy through induction of the dynamin-related protein 1 (DRP1) gene. Remarkably, EM-eNMs selectively target bone tissues through systemic delivery and significantly reverse osteoporotic bone loss in aged mice by enhancing mitochondrial fission and mitophagy, while simultaneously restoring the stemness and osteogenic potential of aged BMMSCs in situ. Taken together, our findings highlight the potential of the EM-eNMs as a targeted therapy to alleviate cellular senescence and age-related diseases.

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Research summary

The paper claims that energy metabolism-engaged nanomedicines can rejuvenate aged stromal/stem cells and alleviate cellular aging. This research addresses the root causes of aging by focusing on mitochondrial function and cellular senescence, which are critical aspects of longevity.

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