Integrated mechanistic models for the study of skeletal muscle protein turnover

点击翻译按钮获取中文摘要

Skeletal muscle has an obvious role in helping us get around. However, an underappreciated aspect of skeletal muscle is that it is a very metabolically active tissue, is a large contributor to our basal metabolic rate, and is the biggest consumer of blood sugar after we have eaten. As such, maintaining a relatively large and metabolically active amount of muscle is very protective in terms of lowering our risk for development of chronic diseases such as overweight/obesity, type II diabetes, and the simple loss of muscle as we age. Muscle growth in adulthood is known as hypertrophy and occurs when muscles are stressed by having to move heavy external loads. The easiest practical example of this is a weightlifter in who, through regularly lifting heavy loads, we can observe an increase in muscle size of their muscles. Interestingly, this occurs for a large part due to the net addition of new proteins within pre-existing muscle cells; this because muscle cells cannot divide and thus they must accrue protein within their existing cellular size to grow. A net accretion of new muscle proteins occurs therefore when the rate of making new muscle proteins - muscle protein synthesis (MPS) - is elevated. We know that nutrients, in particular protein, and weightlifting are both potent stimulators of MPS. However, stimulation of MPS alone is not enough since proteins within muscles are also continually broken down to maintain efficiently functioning proteins. Thus, muscle growth occurs when the rate of MPS exceeds the rate of muscle protein breakdown. In this proposal experiments will be conducted to help understand what processes are involved in increasing muscle size or, viewed alternatively, in slowing/preventing muscle protein loss. We will use, as potent stimulators of MPS, exercise and protein as well as the active components of protein, amino acids in cells grown in petri dishes. To obtain an integrated view we will also, however, compliment the experiments in cells with experiments in humans to ascertain whether the processes we see in cells are operating in a similar fashion. Our findings have substantial implications for understanding how we might slow muscle loss in, for example, aging.