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August 2023

Tetrahedral Framework Nucleic Acids Inhibit Muscular Mitochondria-Mediated Apoptosis and Ameliorate Muscle Atrophy in Sarcopenia

Authors: Xi Yu 1, Yun Wang 2, Liyu Ran 3, Yang Jiang 4, Ming Chen 4, Hao Du 3, Yao Zhang 3, Diwei Wu 3, Xiaona Xiang 5, Jiawei Zhang 6, Ning Jiang 7, Hongchen He 5, Yueming Song 3, Zhou Xiang 3, Chengqi He 5, Zongke Zhou 3, Jiancheng Zeng 3, Yong Xiang 8

Affiliations:

  1. Department of Orthopedic Surgery and Orthopedic Research Institute, Rehabilitation Medicine Center, West China Hospital, Sichuan University, Chengdu 610041 Sichuan, People’s Republic of China
  2. State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041 Sichuan, People’s Republic of China
  3. Department of Orthopedic Surgery and Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu 610041 Sichuan, People’s Republic of China
  4. The Second Affiliated Hospital of Chengdu Medical College, Chengdu 610057 Sichuan, People’s Republic of China
  5. Rehabilitation Medicine Center, West China Hospital, Sichuan University, Chengdu 610041 Sichuan, People’s Republic of China
  6. College of Computer Science, Sichuan University, Chengdu 610041 Sichuan, People’s Republic of China
  7. National Clinical Research Center for Geriatrics, Med-X Center for Manufacturing, West China Hospital, Sichuan University, Chengdu 610041 Sichuan, People’s Republic of China
  8. School of Materials and Energy, University of Electronic Science and Technology of China, Chengdu 611731 Sichuan, China

Journal: Nano Letters - September 2023, Volume 23, Issue 18, Pages 8385-8826 (DOI: 10.1021/acs.nanolett.3c01502)

Sarcopenia is known as age-related muscle atrophy, which influences over a quarter of the elderly population worldwide. It is characterized by a progressive decline in muscle mass, strength, and performance.

To date, clinical treatments in sarcopenia are limited to rehabilitative interventions and dietary supplements. Tetrahedral framework nucleic acids (tFNAs) represent a novel kind of DNA-based nanomaterial with superior antiapoptosis capacity in cells, tissues, organs, and systems.

In our study, the therapeutic effect of tFNAs treatment on sarcopenia was evaluated both in vivo and in vitro.

Results from muscular biophysiological characteristics demonstrated significant improvement in muscle function and endurance in the aged mouse model, and histologic examinations also showed beneficial morphological changes in muscle fibers. In vitro, DEX-induced sarcopenic myotube atrophy was also ameliorated through the inhibition of mitochondria-mediated cell apoptosis.

Collectively, tFNAs treatment might serve as an alternative option to deal with sarcopenia in the near future.

 

Keywords: tetrahedral framework nucleic acids, sarcopenia, muscle atrophy, mitochondria, apoptosis

We found that tFNAs could alleviate muscle atrophy and enhance muscle strength and proved that tFNAs participated in preserving mitochondrial ultrastructures and preventing undesired mitochondrial fission. Furthermore, tFNAs down-regulated cell apoptosis via a BIM/BCL-xL mitochondria-regulated pathway, which is closely related to the pathogenic mechanism of sarcopenia. In summary, our study would shed new light on the understanding of the biological mechanism of tFNAs and provide a novel treatment option for sarcopenia in the clinical setting.

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