Hot Wheels: A Stationary Track for Mice Could Lead to Breakthrough

Newswise — The sight of mice scurrying across the kitchen floor is usually the stuff of our nightmares. But in the lab of Department of Health and Kinesiology Assistant Professor Diego Hernández-Saavedra, running mice indicates progress.

Hernández-Saavedra in 2024 received a $30,000 grant from the Center on Health, Aging and Disability, or CHAD, to study muscle memory. He and his team decided to focus on mice.

“Mice love running. They run like five to 10 kilometers [about 3-6 miles] per night, so a lot. What our studies are trying to do is trying to leverage the fact that mice love running and try to understand whether we can make them healthier,” Hernández-Saavedra said. 
     
The grant Hernández-Saavedra received was part of the CHAD Pilot Grant Program. That program was enabled to support innovative, groundbreaking interdisciplinary research aimed at advancing the understanding of health and wellness, aging disability and the maintenance of a high quality of life.  

According to Hernández-Saavedra, in the initial training phase, mice are trained for four weeks. With this group, researchers try to answer the question of how muscle memory is established. 

In the second phase, mice train, followed by a detraining period where all mice are sedentary. This group tackles the question of whether the muscle memory disappears after exercise cessation. 

In the final training phase, mice are trained, detrained, and once again trained. This cohort answers the question of how prior muscle memory is remembered and recalled by a second exercise training bout, Hernández-Saavedra said.

“We're limited by doing mouse work, but I think it's very interesting because we don't really know how muscle memory works,” he said. “The grant that we received is to study how each cell within the muscle stores the memory and contributes to a better outcome.”

Hernández-Saavedra, born and raised in Mexico, came to the U.S. in 2013 to pursue a Ph.D. at Illinois after receiving his B.S. from the Autonomous University of Queretaro, Mexico. After his Ph.D., he went to The Ohio State University as a postdoctoral fellow in 2018 and returned to Illinois to become a faculty member in 2021.

Hernández-Saavedra’s research focuses on the beneficial effects of exercise to understand the adaptations in key metabolites and lipids in health and disease, the epigenetic mechanisms associated exercise that improve metabolism and bioenergetics, and the transgenerational effect of sedentarism and exercise on metabolism and cardiac function. 

In his post-doctorate work at Ohio State, Hernández-Saavedra studied how maternal obesity can affect the health of babies. Now at Illinois, Hernández-Saavedra is more focused on studying exercise memory, which is understanding whether the body remembers it ever exercised. 

“What our lab is trying to understand is whether our bodies remember prior exercise. For example, if you worked out, in the past, you've gone to the gym, but then you don't go anymore. Four months later, you go back to the gym,” Hernández-Saavedra said. “Do we start from scratch? Do we start from a middle point? Or do they just remember all that and recover really fast to make it stronger, faster and better.”

Hernández-Saavedra explained that his lab studies how the tissue, the muscle, or the liver or the heart, remember prior exercise and how they store information in an epigenetic memory.

“Our research aims to reveal how exercise shapes muscle memory, providing strategies to combat age-related muscle decline, enhance metabolic health and maintain health and mobility as we age,” Hernández-Saavedra said.

For their studies, various groups of mice undergo different exercise training cycles. Some constantly work out, other groups do, but then stop and others workout, stop, and resume again. 

“We use a very interesting strategy,” said Hernández-Saavedra, who credited his students Hank Huang and Clay Weidenhamer for their “tireless” work on the project. “The mice love to work out so we train them. Then we have another group where we train those mice, and then we remove the wheel. And then we see whether the mice, their tissues, specifically the muscle, whether they forget that they ever ran in a wheel.

“They love getting on the wheel,” Hernandez-Saavedra said about the mice. “They love their exercise. And so maybe we should try to be like them a little bit.”