Mechanistic regulation and nutrient modulation of skeletal muscle protein turnover: from cells to humans

Nishimura, Yusuke ORCID: 0000-0001-8225-7675 (2022). Mechanistic regulation and nutrient modulation of skeletal muscle protein turnover: from cells to humans. University of Birmingham. Ph.D.

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Abstract

Skeletal muscle plays a key role in healthy ageing. Skeletal muscle mass is controlled by net protein balance, the difference between muscle protein synthesis and muscle protein breakdown rates, which is regulated by nutrient availability and contractile activity. This thesis identifies and addresses the knowledge gaps in the literature, if filled, may advance the knowledge to regulate skeletal muscle mass. For healthy older adults, it is continuously discussed that dietary protein recommendation should be increased to counteract age-related loss of muscle mass, sarcopenia. Herein, our evidence does not support the growing hypothesis when individuals already adhere to the current internationally recommended dietary protein intake level established by WHO/FAO/UNU. To increase muscle protein synthesis, Cluster Dextrin carbohydrate was co-ingested with meat protein hydrolysate after an acute bout of a whole-body resistance exercise in moderately trained younger individuals. Co-ingestion of Cluster Dextrin activates mTORC1 signalling pathway, but it does not increase postprandial amino acid availability or myofibrillar protein synthesis rate. While muscle protein synthesis and its signaling mechanisms are well established, our knowledge of muscle protein breakdown and its regulatory molecular mechanisms remains in its infancy. The final experimental chapter in this thesis shows that muscle-specific ubiquitin E3 ligases Atrogin-1 and MuRF1 protein, makers of skeletal muscle atrophy, are regulated by different mechanisms in the rapamycin-sensitive mTOR-S6K1-dependent signalling pathway in C2C12 myotubes. Altogether, this thesis improves the understanding of mechanistic regulation and nutrient modulation of skeletal muscle protein turnover and mass.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):