Ageing is associated with a progressive loss of skeletal muscle mass and strength, which ultimately results in a condition termed as sarcopenia. While variable between individuals, typically, muscle mass remains relatively stable until the age of ~50 years, after which it deteriorates at a rate of approximately 0.5-1% per year. However, associated losses in muscle strength occur more rapidly which results in older muscles becoming disproportionately weak. Sarcopenia occurs independently of health status and leads to increased frailty, loss of mobility, an increased risk of falls and fractures, a diminished quality of life, and in some cases, premature mortality.
Maintenance or growth of muscle mass is mainly driven by increased muscle protein synthesis (i.e. the generation of new muscle protein) in response to exercise and consumption of high-quality proteins rich in essential amino acids. However, several studies have shown that elderly individuals have a blunted protein synthesis response following amino acid administration. Similarly, the elderly also elicit a dampened protein synthesis response following resistance exercise, compared to the young. This inability of the elderly to properly respond to growth-promoting (i.e. anabolic) stimuli has been termed anabolic resistance and plays a significant role in the development of sarcopenia. However, while age-associated anabolic resistance is a well-established physiological phenomenon, the precise mechanisms underpinning anabolic resistance are unknown.
At the molecular level, skeletal muscle protein synthesis is primarily regulated by a protein complex called mTOR Complex 1 (mTORC1). The precise mechanisms by which anabolic stimuli activate mTORC1 in humans are not known, however recent studies in cells have identified the lysosome as a being vital for the activation of mTORC1 and thus, protein synthesis. The lysosome is the organelle within cells responsible for breaking down proteins and recycling the amino acids (i.e. the building blocks of proteins).
Lysosomes have the ability to move from one part of the cell to another, and based on recent evidence, this lysosomal movement (i.e. lysosomal trafficking) in itself, seems to be vital for the activation of protein synthesis. Thus, age-associated impairments in the movement of lysosomes within aged muscle cells, may represent a possible explanation for the development of anabolic resistance in elderly individuals.
Therefore the primary aim of this project was to examine the involvement of lysosomal movement in the regulation of protein synthesis in human skeletal muscle in the context of age-associated anabolic resistance.
