The National Institute on Aging of the National Institutes of Health has awarded Associate Professor of Physiology Robert Wessells, Ph.D. $1.68 million to continue studying the molecular genetic mechanisms that underlie the benefits of exercise, considered a powerful protective factor against age‐related diseases, including heart disease, cancer and diabetes.

Dr. Wessells is the principal investigator for “Octopamine Controls Adaptation to Endurance Exercise in Drosophila.” This is the first grant renewal for the project, which was initially funded by the NIA in 2018.

The Wessells laboratory published the first fly exercise paper in 2009, and developed the first exercise machine for Drosophila, or fruit flies, using the animal model to study mechanisms of adaptation to regular exercise.

“This particular project built off of a discovery we made a few years back that adaptations to regular exercise require a certain cluster of neurons in the fly brain. Those neurons produce a fly equivalent of norepinephrine, and it turns out that if you use genetic tools to activate those neurons for one to two hours a day, they can cause increased speed, endurance and cardiac performance even in flies that don’t exercise,” Dr. Wessells said. “However, it would be hard to use this strategy in mammals, like humans, because drugs that increase norepinephrine levels would cause hypertension.”

In the previous grant round, they examined what octopamine is activating in the fly muscle that causes increased performance and slower aging in muscle.

“We found several such genes in flies, and our collaborators found that these exercise-response genes are also required for exercise adaptations in mice. In the renewal portion of the grant, we plan to figure out how the genes we identified work together in a regulatory pathway and extend our understanding to how they work in other organs, such as brain and fat,” he said.

The renewal portion of the grant includes a translational aim in which Dr. Wessells will test the ability of virtual reality-based stimuli to stimulate exercise response genes in humans. “We hope this might lead to virtual exercise programs that would allow patients who are forced to endure long sedentary periods to maintain metabolic health through virtual stimuli.”

“I am happy that the work is being recognized and that the review panel would like to see it continue. I am also excited to recruit new lab members and continue growing the lab,” he said. “We have begun branching out in recent years to also study the potential therapeutic uses of the exercise-response genes we have been studying. We feel they could be therapeutic targets for diseases that reduce mobility and make exercise difficult or impossible, such as mitochondrial or neurodegenerative diseases.”

“This National Institute on Aging award builds upon previous discoveries made by Dr. Wessell and his research team here at Wayne State University,” said Ezemenari Obasi, Ph.D., vice president for research & innovation. “With the help of this renewed funding from the NIH, Dr. Wessells will continue his research that has found ways to stimulate certain regions of the brain that can offer exercise-like benefits in sedentary animals, and moving forward, may help people with illnesses or injuries that restrict their movement. I look forward to the potential impact of this research.”

The project number for this National Institute on Aging of the National Institutes of Health award is AG059683.