Integrated Regulation of Bone and Muscle Metabolism by Simulated Microgravity
Henry J. Donahue, Ph.D.
Virginia Commonwealth University
The long-term goal of this project is to understand the structural and functional relationship between muscle atrophy (i.e., sarcopenia) and bone loss (i.e., osteopenia) which occurs as a result of extended exposure to the spaceflight environment.
1) Examine the time course for structural, functional, and molecular changes occurring in muscle and bone in response to mechanical unloading;
2) Examine the effect of inhibiting, or exaggerating, unloading-induced muscle loss on unloading-induced bone loss;
3) Examine the effect of inhibiting, or exaggerating, unloading-induced bone loss on unloading-induced muscle loss; and,
4) Evaluate potential therapeutic strategies for prevention of muscle and bone loss during unloading.
Upon completion of the specific aims, and based on the experimental approaches, the researchers will recommend specific therapeutic strategies and countermeasures that target muscle and bone as an integrated unit and respect their inherent interdependency. To accomplish these objectives, the researchers will use hindlimb suspension, a well established in vivo model of simulated microgravity unloading.
The overall hypothesis is that unloading-induced osteopenia is at least partially dependent on unloading-induced sarcopenia and, conversely, unloading induced sarcopenia is at least partially dependent on unloading-induced osteopenia.
The rationale for this project is that there has not been a comprehensive and simultaneous examination of the effects of unloading on both muscle and bone. Understanding how these two systems respond to simulated microgravity will allow for the development of effective countermeasures to preserve astronaut health during missions and upon return to Earth. The research team assembled has extensive experience examining, both in vitro and in vivo, bone and muscle response to loading and unloading. This collective expertise will bring a unique and valuable perspective to the project.