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Role of Muscle Loading on Mechanisms of Protein Translation and the Impact on Unloading-Induced Atrophy

Principal Investigator:
Kenneth M. Baldwin, Ph.D.

University of California, Irvine

Exposure to the space environment causes muscle wasting and alters the muscle fibers involved in contraction. Studies suggest that these changes are caused by an imbalance between the synthesis and degradation rates of muscle proteins, and Dr. Kenneth M. Baldwin is identifying how space conditions alter the body’s mechanisms that regulate protein levels. Through an animal study, he is developing a resistance-training program to reduce muscle atrophy and muscle fiber changes.

NASA Taskbook Entry

Technical Summary

In this project our goals were two-fold:
  1. Ascertain a better understanding of the cellular factors that cause muscle atrophy;
  2. Develop a resistance training protocol that can successfully create an anabolic state in the muscle that could serve to counteract the catabolic state that is associated with models of muscle unloading.

Our findings suggest that in rapid muscle atrophy models, there are fundamental reductions in the ability of key skeletal muscle genes to transcribe the message and the cell machinery to translate the message into protein. This deficit occurs in the face of elevations in the protein degradation systems that cause the normal breakdown in these proteins. Such an imbalance results in net protein loss in the muscle, thereby causing the muscle cell to become smaller. Resistance training improves the status of the muscle by slowing down the protein breakdown process while at the same time enhancing the muscle to synthesize new contractile protein. We are confident that by selecting the right prescription of resistance training, we will be successful in preventing the muscle wasting that occurs in space travelers.

We have identified useful and practical resistance training modes that improve the size of the muscle. Furthermore, we have identified likely processes impacting the imbalance in protein mass that occurs in response to skeletal muscle unloading. We have also identified the importance of growth factor expression that affects protein translational processes, which are important in maintaining positive protein balance in the face of unloading states. The goal is to use this information and design a resistance training prescription that can be effective in preventing muscle atrophy in the next funding period 2004-2008.

Specific Aims
The primary aims were to contrast the effectiveness of different contraction modes for inducing hypertrophy of rodent skeletal muscle using a computer driven training devise. Muscles were activated with 40 contractions for each training session, with each contraction consisting of 2 seconds with appropriate rest intervals between each contraction and each set. The modes of contraction were of the isometric type, concentric type, e.g. shortening actions, and the eccentric type, e.g, lengthening actions of the same initial force generation. These experiments used muscle weight, total protein accumulation, insulin-like growth factor-1 and total RNA as key outcome variables.


Earth Applications

The problem of sarcopenia or muscle wasting associated with aging affects every human being over 40 years of age. Our research on the mechanisms of muscle atrophy and the use of resistance exercise, in the face of muscle unloading, will provide practical knowledge and useful strategies for ameliorating or slowing this critical health problem.

This project's funding ended in 2004