Muscle Protein Turnover: Methodological Issues and the Effect of Aging

Investigation of sarcopenia should include the measurement of muscle protein synthesis and breakdown because reduced muscle mass occurs only when muscle protein content is reduced. Protein content of a tissue is determined by the balance between synthesis and breakdown. Whole body measurements are inappropriate for determining the small changes in muscle protein synthesis and breakdown, since muscle contributes less than 30 percent to the whole body protein turnover. The measurement of mixed muscle protein synthesis in humans supports the animal data, which demonstrates that there is a decline in muscle protein synthesis with age. Resistance exercise stimulates mixed muscle protein synthesis rate in both the young and the old, although this is not demonstrated when myofibrillar protein synthesis is measured. Muscle is composed of several types of proteins, and their turnover may be differentially regulated. It is important, therefore, to measure the turnover of specific proteins such as myosin and actin, which are important contractile proteins. Recently, techniques have been developed to measure the synthesis rate of myosin heavy chain (MHC) in humans. In addition, the application of quantitative polymerase chain reaction (PCR) allows measurement of the steady state mRNA levels of various isoforms of MHC. These measurements, in combination with measurement of the synthesis rate of MHC, will allow us to understand the molecular regulation of specific proteins such as myosin. The important question is to determine whether the decline in muscle protein synthesis is genetically determined or secondary to inactivity, nutritional, hormonal, or other age-related alterations in body functions, and whether muscle wasting is reversible. Intervention studies such as exercise-training, hormone replacement, and nutritional supplements will allow us to determine if changes in protein synthesis are reversible.