Understanding how cells adapt after exercise
Xuansong Mao of the Fralin Biomedical Research Institute at VTC will use a Lyerly Postdoctoral Excellence Award to research the role of exercise in Alzheimer’s, metabolic conditions, and age-related cognitive decline.
As a professional sprinter for more than 10 years, Xuansong Mao specialized in the 100-yard dash. When Mao wasn’t racing, he was training for a race.
As that chapter of his life came to a close, Mao hoped the next would still revolve around running.
In a way, it does. But now, he watches mice run.
“I always thought I would end up as a coach or PE teacher,” said Mao, who is now a postdoctoral associate at the Fralin Biomedical Research Institute at VTC. “But when I realized exercise was a meaningful health intervention, I decided to do more research about the biological mechanisms of exercise that can induce these positive adaptations.”
Now a postdoctoral researcher in the lab of Professor Zhen Yan, he studies the molecular pathways through which exercise yields its health benefits. His current projects focus on two interconnected questions: How does physical activity protect the aging brain from cognitive decline? And how does endurance training contribute to skeletal muscle adaptation?
Support from a 2025-26 Postdoctoral Excellence Award will allow Mao to continue exploring these questions. The annual award recognizes postdoctoral trainees at the Fralin Biomedical Research Institute whose research proposals show potential for novel scientific contributions.
In one experiment, mice are presented with two identical objects. They naturally spend time exploring both objects. Two hours later, the same mice are again presented with two objects. This time, one object is from the prior task, and one is novel.
A healthy mouse will remember the familiar object, lose interest, and spend more time investigating the new object. But mice with memory deficits will spend similar amounts of time investigating both the new object and the familiar object. These memory deficits begin to appear in 14-month-old mice, the equivalent of a 45- to 55-year-old person.
But Mao’s research has revealed that after voluntary endurance training, with some mice running up to 10 kilometers per day, the aged mice began to perform significantly better on the memory task, suggesting that endurance exercise like distance running can protect against the memory decline that naturally occurs with age.
Beyond cognition, Mao’s recent work in the Yan lab explores the impacts of exercise on skeletal muscle. For decades, exercise physiologists have accepted that regular exercise activates the enzyme 5’ adenosine monophosphate-activated protein kinase, or AMPK. AMPK helps muscles produce more mitochondria — the cell’s energy-generating structures — thereby increasing exercise capacity. Past studies in the Yan lab have established that AMPK is vital to the process by which exercise boosts mitochondria quantity.
Mao is now exploring whether, in the absence of AMPK, mice can still improve their cardiorespiratory fitness and endurance capacity through training. Through further research, Mao hopes to refine this study as he continues to explore preliminary findings that challenge the long-standing belief that enhanced mitochondrial content and activity in skeletal muscle are necessary for improved endurance capacity.
Mao looks ahead to a future where researchers can develop molecules to mimic the cognitive and metabolic effects of exercise for those who are physically unable to exercise. But for those who can, Mao said exercise remains a free to low-cost intervention that can substantially lower future disease risk.
