Filling in the blanks on muscular aging

With an eye on medical school and an interest in human aging, biochemistry concentrator Anson O’Young ’22 realized he was lacking something that probably would help him in his future career path – research experience. 

“Before this summer, I had never been in a lab before,” O’Young says. “I had never experienced research like this and because I want to go to med school, I wanted to get a sense of it to see if it’s what I want to do.”

He wanted to spend the summer before his senior year working in the lab of Gregorio Valdez, PhD, the GLF Translational Associate Professor of Molecular Biology, Cell Biology, and Biochemistry, who investigates molecular functions related to aging.

But O’Young, who’s from Nashua, NH, needed a stipend to make living and working in Providence possible. So he applied for an Undergraduate Teaching and Research Award, or UTRA, which supports a Brown student for 10 weeks of full-time work in a faculty member’s lab. 

“I have a strong interest in the medical field, especially on how the human body changes with age,” O’Young says. “Since projects in the Valdez lab focus on molecules that exist to preserve and restore the function of the nervous system and skeletal muscles during normal aging, it was the perfect place for me to be.”

The neuromuscular junction (NMJ), responsible for converting electrical impulses generated by the motor neuron into action by the muscle fibers, has three elements: the motor neuron, the muscle fiber, and the less known perisynaptic Schwann cell (PSC). For his UTRA project, O’Young analyzed and measured the features of aged PSCs in mice.

“In this particular project, the tools we use to label each element of the NMJ are different colored fluorescent proteins,” says Robert Louis Hastings, PhD, a second-year postdoctoral research associate in Valdez’s lab who has mentored O’Young since late last spring. “The fluorescent proteins allow us to distinguish the PSCs from the other parts of the NMJ and once we can make that distinction, we can analyze the structure of the cells at different ages.”

In the NMJ, the synapse between the motor neuron and the muscle fiber allows for smooth signal transition from the brain to the muscle. The PSCs’ roles include NMJ maintenance, transmission, and regeneration. As we age, the neuromuscular system starts to break down in several ways, such as the degeneration of individual synapses, diminishing the brain’s control of the muscle. The aging process has been well documented for the motor neuron and the muscle, but not so for the PSC.

“By looking at the PSCs, we can potentially provide novel insights into understanding the degeneration process in old age,” O’Young says. “The data we collected will only add to what we already know about muscular degeneration in aging. By studying muscle samples from mice at various ages, we hope to determine whether or not there is a correlation between changes in PSC morphology and other NMJ components in mice at various stages in life.”

O’Young is Hastings’ first undergraduate mentee, and since he plans to continue as an academic researcher, it’s a fundamental aspect of his own training that he finds very rewarding. It’s clearly a win-win for both of them.

“It was great going through the initial process of training with Anson,” Hastings says. “I enjoyed teaching him to identify the different cell types and take the measurements he needed. Now he’s analyzing about 60 NMJs a week and we review what he’s done and I answer any questions he has, especially because the changes he’s witnessing can be complex and hard to analyze.”

Before he graduates, O’Young will continue to work with Hastings to publish a paper with their findings and present at a conference.

“I like being on the cutting edge of this research,” O’Young says. “It’s very meaningful to me to feel like I’m making an impact in advancing our scientific knowledge and hopefully relevant to what I want to do in the future, helping people in need.”