ABSTRACT

Sarcopenia results in progressive deterioration of skeletal muscle with age, leading to increased risk of frailty and poor health outcomes. As the incidence of sarcopenia is expected to rise in the elderly population, identifying cost-effective interventions that improve muscle formation and health is a major public health challenge. Efforts to identify potential drugs have been hindered by sarcopenia's slow progression in clinical studies. Microgravity is known to accelerate the process of aging and muscle disuse. Therefore, by taking advantage of the microgravity environment aboard the International Space Station National Laboratory, it will be possible to develop a tissue engineered model of sarcopenia. Once validated, this model can be used to study the progression of muscle deterioration and serve as a useful platform for testing potential treatments in a short period of time. The overarching hypothesis is that engineered skeletal muscle in microgravity mimics relevant features of sarcopenia. This platform has the potential to improve the quality of life of patients with sarcopenia or other muscle wasting diseases. In addition to the anticipated societal benefit of the research, the project includes educational outreach activities that have the goal of increasing the exposure and interest of Veteran college students from a Hispanic-serving local community college to pursue careers or majors in STEM areas. These activities include teaching bioengineering concepts in a STEM seminar series; developing curriculum and teaching a bioengineering workshop; and offering science research internships in the laboratory of the principal investigator.

This project proposes to design and characterize an in vitro engineered skeletal muscle platform in microgravity to model sarcopenia. The model will be validated based on genomic and proteomic features, as well as by the remodeling of the extracellular matrix. The first two aims involve developing the engineered muscle model on Earth and then taking advantage of a 7-day experiment on the International Space Station to induce the tissue changes seen in sarcopenia. Once the sarcopenia model has been validated, it will be applied to demonstrate the feasibility of testing candidate drugs for treatment of sarcopenia. If successful, the proposed studies will significantly impact the pace of identifying drug candidates for effective treatment of sarcopenia, by serving as an important intermediate step prior to clinical trials. In addition, the validated model will be a novel system to study the pathology of muscle degradation as a result of sarcopenia.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

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