Jacqueline I. Perticone, B.S.
Loss of muscle mass with advancing age, disease or lifestyle has a profound influence on healthcare and society. Our laboratory uses hindlimb suspension in rodents to better understand loss of muscle mass occurring with disuse in an effort to design specific interventions that may be suitable to maintain muscle health and function in a number of populations.
It is well-known that loss of muscle mass with reduced activity results from a slowdown in the muscle’s production of new proteins, which can negatively affect the structure and function of skeletal muscle. Although there may be numerous reasons as to why this happens, our lab has shown that the reduced protein synthesis seems to be equally distributed to most of the cellular proteins, not exclusively within the structural proteins that support function and mass. Since protein synthesis is a biologically expensive function, the uniform reduction of protein synthesis may indicate that the energy necessary to support the manufacture of proteins has been compromised with disuse. Thus, a reduction in the capacity to generate the energy to make proteins would dramatically limit the ability to make proteins under most conditions.
The mitochondria, the major powerhouses of the cell, largely support protein synthesis under normal conditions. Since the mitochondria are also made up of proteins, it stands to reason that any deficit in the manufacture of mitochondrial proteins would dramatically affect the capacity of the cell to maintain the energy necessary to maintain its function. To date, no studies have specifically assessed the impact of disuse on mitochondrial protein synthesis. The purpose of the proposed study will be to determine the impact of multiple bouts of unloading and reloading on mitochondrial content and concentration in gastrocnemius muscles of rats.
To complete these studies, we will assess mitochondrial protein synthesis and content during disuse (using hindlimb suspension techniques) and the passive recovery (normal ambulation) from disuse in postural muscles of the rat. Mitochondrial protein synthesis will be measured over a 24-hour period using a robust deuterium oxide methodology, which allows us to isolate and evaluate specific sub-fractions in the cellular compartment, as well as estimate pool size (content) in the muscle. Furthermore, we will assess the impact of moderate resistance exercise (active) on this important organelle during the passive recovery phase from unloading. We will also assess how the mitochondria are affected by a subsequent bout of unloading following recovery to see if repeated exposure to disuse adversely affects adaptations of mitochondria in muscle. The proposed work will allow us to assess, for the first time, the impact of muscle disuse on muscle mitochondrial protein synthesis and content, as well as how the muscle responds to rehabilitative passive and/or active recovery. Results of our studies will have important implications for the design of specific strategies to support muscle mass during periods of disuse or disease, which may assist in the prevention of atrophy and functional dependence under a variety of conditions.
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