Muscle extracts from Antarctic fishes Trematomus bernacchii and T. Newnesi enhance myofiber regeneration and muscle function through mTOR signaling

• The muscle extracts of Antarctic fish species, Trematomus bernacchii and Trematomus newnesi , exhibit not only the ability to promote myofiber formation but also demonstrate effectiveness in restoring grip strength during muscle regeneration. • The extracts derived from Antarctic fish, Trematomus bernacchii and Trematomus newnesi , have been found to enhance mTOR activity. • Bioactive substances such as taurocholic acid and its potential derivatives, along with denatorium, have been identified and annotated through liquid chromatography-mass spectrometry and Global Natural Product Social (GNPS) molecular networking. Muscle regeneration and functional restoration are crucial for patients with sarcopenia. Antarctic fish, which are well-adapted to extreme conditions, offer potential pharmacotherapeutic insights. Our study assessed muscle extracts from Trematomus bernacchii (TB) and T. newnesi (TN) in a BaCl 2 -muscle injury mouse model. TB and TN extracts notably enhanced myofiber formation during muscle regeneration, showing potent proregenerative properties. Grip strength restoration was significantly improved, accompanied by increased expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha and mitochondrial content, which are vital for post-injury recovery. The activation of the mammalian target of rapamycin and insulin-like growth factor 2 muscle enhancer activity underpinned these effects. Ultra-performance liquid chromatography-mass spectrometry and Global Natural Product Social analysis annotated taurocholic acid and its derivatives, along with denatorium, as bioactive substances that contribute to muscle enhancement. These findings have implications for therapeutic development for muscle regeneration and functional recovery in patients with musculoskeletal injuries and sarcopenia.