Understanding Exercise and Muscle Physiology at the Molecular Level

Members of the Molecular Muscle Physiology Laboratory are (from left): Yair Pincu, Kai Zou, Heather Huntsman, Marni Boppart, Ziad Mahmassani and Mike De Lisio.

The benefits people receive from exercise are reinforced by new research, but this growing emphasis also brings about questions, such as the effect of exercise on the body. Marni Boppart studies these questions and more at the Molecular Muscle Physiology Laboratory she directs at Beckman.

The benefits people receive from exercise, such as improved cognition over the lifespan and disease prevention, are reinforced by new research and promoted to the public on an almost daily basis. But this growing emphasis also brings about questions, such as its impact on the body and whether exercise alone is enough to counteract age-related conditions.

Beckman Institute researcher Marni Boppart addresses these questions and others at the fundamental levels of cells and molecules in work at the Molecular Muscle Physiology Laboratory she directs at Beckman.

Boppart has created a unique research line as she applies cell and developmental biology to kinesiology in ways that haven’t been done before. Her goals are to gain a greater understanding of the effects of exercise and mechanical strain on muscle, and to translate that work into novel interventions that could serve to complement exercise when it comes to preventing the muscle loss that comes with aging.

The Molecular Muscle Physiology Laboratory is unique for its study of musculoskeletal remodeling and growth in response to exercise and mechanical strain, and as one of the few places where researchers have the ability to manipulate muscle stem cells and investigate the role they play in those processes.

Boppart, who earned a Sc.D. in Applied Anatomy and Physiology from Boston University, came to Illinois in 2000 as a postdoctoral researcher in the Department of Cell and Developmental Biology. She is now an Assistant Professor in the Department of Kinesiology and Community Health and full-time member of Beckman’s Bioimaging Science and Technology group.

We are very excited because this work is an important step towards developing effective interventions that can prevent the loss of muscle that occurs with aging and disease.
– Marni Boppart

In her research Boppart has been able to develop new methods for extracting stem cells from pre-clinical models and use them to study their effects on muscle in response to exercise. It is work that has led to a growing list of projects, papers, collaborators, and new research opportunities.     

“I love coming into work every day because it is so exciting,” she said. “I try to keep our work focused and not get too far out of my realm. But sometimes it’s hard. Where do you set your limits in terms of how these stem cells interact with these other tissues?

“We’re one of the only labs in the world that knows how to isolate these stem cells and manipulate them in a culture,” Boppart added. “Of course we want to learn everything we can about these cells, inject them, and see what happens.”

One example of what’s been happening was reported in a recent paper in the journal PLoS ONE that drew national attention for the discovery that a single bout of exercise in mice led to an increase in mesenchymal stem cells (MSCs) that reside in skeletal muscle. The findings have relevance for understanding the critical links between exercise and whole body health.

“We think that it’s very important for us to translate this work to the human condition,” Boppart said. “We are very excited because this work is an important step towards developing effective interventions that can prevent the loss of muscle that occurs with aging and disease.”

Muscle-derived mesenchymal stem cells (or mMSCs) play a role in regeneration response to injury or disease in skeletal muscle, and Boppart’s lab is leading the way in the study of them. The PLoS ONE paper emphasized the importance of understanding the processes underlying skeletal muscle regeneration.

“What we’ve been able to show in this paper and our current work is that mMSCs are not directly contributing to muscle growth, but do in fact secrete a variety of different factors that positively impact muscle regeneration and growth” Boppart said. “The cells usually respond to injury but in the case of exercise what we think, and this is a very novel phenotype for these cells, is that they secrete the factors specifically in response to mechanical strain.”

Boppart’s research for many years has focused on the a7 integrin receptor – a molecule that mediates connections between cells and tissues – for its role in biological processes such as protecting against injury and regulating exercise-induced muscle growth.   

“We’ve found that the a7 integrin and these stem cells, which are usually positively correlated, are both markedly decreased with age,” she said. “And so we’re trying to determine if we can somehow revitalize stem cell proliferation and function in some way.”

That will lead, Boppart said, to the next step in her work, which is translating the research findings into ways that could help people, such as interventions that prevent or reduce muscle loss.

“I think our next big major goal after understanding that the cells are there in response to exercise is to understand what happens if you don’t have those in the muscle anymore,” she said. “Does exercise help revitalize some of those cells?”

Boppart said early work on that question appears to show that exercise alone is not enough. That’s why future interventions for muscle loss will probably include some kind of drug therapy.

“What might help is the addition of the a7 integrin,” Boppart said. “What we’re trying to do is enhance or restore the presence of the a7 integrin, which may then allow for these stem cells – whether they are endogenously injected or they are naturally in that environment – to accumulate once more. We’re looking at chemical compounds that can increase the a7 integrin and therefore revitalize stem cell function.”

Boppart said exercise is important in preventing the aging process but it doesn’t completely eliminate the muscle loss that occurs with aging.

“If you have muscle loss you have dementia because there is a tight correlation between the two,” she said. “The aging process can be delayed by exercise but not entirely prevented. So we’re trying to add a spark that allows you to age better longer.

“I think we’ve decided that we should use exercise as a model for understanding how we can intervene with the aging process. There are people who exercise their whole lives and still have muscle loss. Clearly we’ve got to do something to supplement that exercise effect.” 

Boppart has several collaborations, both on campus and off, including one with her husband and Beckman colleague, Stephen Boppart. They have tracked bone marrow-derived stem cells in skeletal muscle and skin and have been able to identify the specific cell type in skin migrating from the bone marrow as dendritic cells.

A recent collaboration with Justin Rhodes of the Biological Intelligence research theme involves neurogenesis, or the creation of new brain cells.

“We’re very excited about the possibility that the stem cells in muscle are secreting factors in response to exercise that may enter into the circulatory system and also enhance neurogenesis,” Boppart said. “Prior to talking with Justin I was not interested in brain and cognitive function but there clearly are some correlations between muscle health and brain function.”

That collaboration also has the potential for future beneficial interventions, in the area of cognitive health. In addition, Boppart said, her lab is finishing a study that focuses on the ability of mMSCs to directly and indirectly facilitate vessel growth in muscle. The results could provide insight into how a stem cell-induced increase in the diameter of existing arterial vessels might also facilitate tissue quality in response to exercise. 

The newer projects and collaborations may require more students and more room for her lab, which is currently sharing space with Stephen’s lab.

“We have several proposals in progress right now,” she said. “Things are taking off so quickly.”