Muscle atrophy caused by weightlessness is similar to the muscle wasting caused by disuse on Earth. Dr. Marc T. Hamilton is examining the effects of muscle disuse through human trials involving one-leg bicycle exercises, and he is investigating the effects of muscle disuse on genetic expression in rats after periods of exercise and inactivity. This research will provide knowledge of the physical effects of muscle disuse and is measuring how all of the approximately 35,000 genes in the human genome are adversely affected by physical inactivity.
Overview
Genomics of Human Skeletal Muscle During Bed Rest and Exercise
Principal Investigator:
Marc T. Hamilton, Ph.D.
Organization:
University of Missouri
Technical Summary
Reduced use of weight-bearing skeletal muscles during microgravity and sedentary life on Earth causes unhealthy and potentially dangerous consequences. For example, leg muscles atrophy and also have a profound reduction of lipoprotein lipase activity (an enzyme in the blood vessels of muscles with a protective effect against lipoprotein risk factors for coronary heart disease). It is likely that an unbiased determination of the global expression pattern of the human genome with microarrays will reveal many muscle mRNAs increasing and decreasing, including mRNAs that heretofore have never even been hypothesized to contribute to the microgravity or sedentary phenotype.
Additionally, large scale genomic studies are likely to begin to reveal clusters of related mRNAs that provide clues as to the sets of genes orchestrating some of the cellular signaling, transcriptional changes, cellular growth and metabolism. This project will build upon recent experience established from microarray studies of hindlimb suspension, endurance exercise and muscle fiber type that support the statements described above. The effects of bed rest and one-leg exercise (as a countermeasure to attenuate the effects of inactivity) on the soleus muscle of six men and six women will be studied.
Using state-of-the-art microarray methodologies, this project will measure the expression of approximately 12,000 full-length. Sequence verified mRNAs and approximately 3,000 of the most abundant muscle ESTs. This project is being proposed by a laboratory already using microarrays in the study of muscle physiology, in collaboration with a bioinformatics laboratory, a physical therapy laboratory focused on muscle function, a physician-scientist studying muscle diseases and a core laboratory for microarray development. This study is likely to discover novel candidate genes and clusters of related genes potentially responsible for the unhealthy responses to reduced muscle use during physical inactivity.
This project's funding ended in 2005