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UVa research: Weightlifting rodents offer hope for humans

The workout regimens of hungry mice may lead to improved gym rat exercise routines and better health for older adults, thanks to a University of Virginia School of Medicine researcher who developed a mouse gym in his garage.

Zhen Yan, an expert on exercise and its impacts at the cellular level, said the new research method allows lab rodents to work out on their own schedules and without human intervention. That helps researchers determine how weight-bearing exercises affect the mice, and probably humans — from their muscles and organs to cells and genes.

Yan is director of the Center for Skeletal Muscle Research at UVa’s Robert M. Berne Cardiovascular Research Center. He recently found a link between exercise and surviving acute respiratory distress syndrome, a major cause of death from COVID-19.

“When we’re talking about the benefits of exercise, everyone understands how important it is but the reality is we know very little about how it impacts the body. We only know the tip of the iceberg,” Yan said. “The more we understand, the more we can try to energize the general public to exercise and take advantage of the information we’ve learned to improve health.”

The study of rodents running wheels in their cages helped researchers to pin down the advantages to aerobic exercises such as walking and running, but Yan said weight-bearing exercises are not as well understood from a metabolic angle.

“We know a good deal about aerobic exercise. We know a lot because of the animal model. You can measure the effects of aerobic exercise on rodents who are running in their cages and doing so on their own,” Yan said. “What we don’t have is a good model for weight training that doesn’t involve a human intervention.”

Methods used to study rodents and weight training tend to over-develop muscles and require the animal to use the muscle group all of the time, Yan said.

“The research involves a procedure that is difficult, tedious and requires human handling and it results in the muscles being worked 24-7,” he said. “You don’t lift weights for 24 hours a day, and it’s hard to measure how the exercise is beneficial.”

Like most research, the problem led to inspiration, which led to exploration, which led to discovery.

“I worked in the garage and made prototypes, trying to figure out how this could work,” Yan said. “I fabricated a cage top that took advantage of the feeding behavior of rodents at night. We put a plate on a hinge attached to one side and food.”

Without humans forcing them to pump iron or use a muscle group, the rodents went scurrying about their nocturnal business. That business includes eating, and that’s where Yan’s cage top came into play.

To get to the nuggets of food, the rodent would need to lift the cage top using a squat-like maneuver, same as athletes and gym members do. The impact of the exercise on rodent legs could then be extrapolated to their human counterparts.

“We’ve discovered that the movements build muscle very consistent with the way humans build muscle in the gym,” Yan said.

Those muscle impacts also led to muscled mice with thicker bones and improved ability to utilize insulin.

“As we age, we add more body fat, our bones grow weaker and we are at greater risk of diabetes,” Yan said. “This tells us that we may be able to use weightlifting to help in the treatment of diabetes and address problems of aging such as osteoporosis and loss of muscle mass, things that concern everyone over 40.”

Learning how weight-bearing exercise impacts the body at the cellular level also could lead to medications down the road.

“We understand why exercise is very important, but we know very little about exactly what it does, and this helps us see the impacts more clearly,” Yan said. “I imagine we will never generate a pill to get all of the benefits of exercise and exercise will still be the best alternative compared to pharmacological intervention. But we may be able to develop drugs that can mimic the benefits of exercise in some ways to help those who cannot exercise because of medical problems or disabilities.”

Yan said the research is just beginning.

“The findings are truly the tip of the iceberg,” he said. “We hope many researchers in the scientific community can use this model to unveil the effective exercise secrets to benefit the general public.”


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