Novel approaches to reduce muscle atrophy and metabolic dysfunction in older adults during physical inactivity

Background

Hospitalizations for disease, injury, and/or surgery in older adults are likely to impair physical mobility and, therefore, the older adults capacity to be physically active both during hospitalization and beyond. The resulting sedentary lifestyle is likely to be accepted as the "new normal", ultimately increasing the risk of skeletal muscle and metabolic dysfunction (e.g. insulin resistance and sarcopenia). Muscle atrophy and insulin resistance are an unfortunate consequence with disuse in older adults. We have observed with our bed rest studies in healthy older adults that in addition to muscle and metabolic changes, we notice increased skeletal muscle inflammation, impaired glucose uptake signaling and an upregulation of enzymes related to de novo ceramide biosynthesis. The accumulation of ceramide, a toxic lipid intermediate, can disrupt glucose homeostasis and impair muscle growth. Insulin sensitizers (common diabetic glucose lowering medications) not only improve insulin sensitivity but may be able to attenuate muscle loss in insulin resistant adults through a mechanism that may involve ceramide synthesis. This might be a useful preventive strategy to maintain muscle and metabolic health during a period of physical inactivity in older adults has not been investigated. Therefore, we have proposed to conduct a clinical study in healthy glucose tolerant older adults to test if specific insulin sensitizers during bed rest will attenuate insulin resistance, muscle loss and accumulation of ceramides. These findings will be foundational in the development of novel treatments to prevent insulin resistance and muscle atrophy in older adults during disuse periods.

Student Role

The intern will work with Dr. Drummond on the first day to identify the specific question within the current project to be addressed and will provide guidance throughout the program. Data will be collected from frozen tissue samples or from current clinical studies collected during the summer. The student will be trained by myself and a current student/fellow on a specific laboratory technique/skill set in order to contribute to the data collection process. Concurrently, interns will assist lab members with mouse and human experiments.

Outcomes

The student will:

  • Learn different research models of physical inactivity to test in mouse and humans
  • Gain exposure to a translational research program: active experiments in animal and clinical research
  • Gain knowledge on cellular mechanisms that contribute to muscle atrophy and insulin resistance in humans
  • Gain experience presenting an article or current collected data at a research lab meeting
  • Be integrated into a cohesive research team seamlessly working together helping each other out on projects.

Benefit: Lab experience will result in an abstract, poster presentation, and eventual co-author publication.

Micah Drummond
Associate Professor

Physical Therapy & Athletic Training
College of Health

Training is a very important component to a healthy research laboratory and a trait that is regularly practiced in my lab. This has resulted in several training-type research grants for my current students/fellows. I typically meet one-on-one with all my students and fellows in my lab 1x a week to discuss projects, short term/long term goals, barriers, and, in general, "how things are going". I typically work hands on with students in the lab but more recently I have given this wonderful opportunity to my senior fellows or students who are incredible at teaching/training new skill sets. We also have a lab meeting that meets once a week so that the intern has an opportunity to freely engage in a non-formal discussion of current research. This is also an opportunity for us to go over a recent article presented in journal format (student/fellow presentations rotating week to week). For the intern, I also offer clinical shadowing opportunities. This would occur periodically during the internship and would occur at the Center for Clinical and Translational Sciences at the Institution. This is an opportunity to interact with other medical professionals such as nurses and physicians.