Tetrahedral framework nucleic acids inhibit muscular mitochondria-mediated apoptosis and ameliorate muscle atrophy in Sarcopenia

Sarcopenia is known as age-related muscle atrophy that affects more than a quarter of the elderly population worldwide. It is characterized by progressive decline in muscle mass, strength and performance, which deteriorated life quality and increased mortality eventually. Up to date, clinical treatments in sarcopenia are limited to rehabilitative interventions and dietary supplements only, without any effective therapeutics. In this study, tetrahedral framework nucleic acids (tFNAs) were utilized to treat sarcopenia both in vitro and in vivo. tFNAs participated in the maintenance of mitochondria energy metabolism by regulating mitochondrial outer membrane permeabilization and the preservation of mitochondrial ultra-structures by inhibiting excessive mitochondrial fission. tFNAs also down-regulated cell apoptosis via BIM/BclxL mitochondria-regulated pathway, which is closely related to the pathogenic mechanism of sarcopenia. Furthermore, tFNAs altered the size and arrangement of muscle fibers to enhance muscle stiffness in sarcopenia mouse model. Altogether, these findings proved that tFNAs were effective in ameliorating age-related muscle atrophy and hence could be a promising treatment option for sarcopenia in the future.