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Researchers secure $1.1M in NIH funds to study effects of exercise on chronic health conditions



INDIANAPOLIS — The National Institutes of Health has awarded grants totaling more than $1 million to two researchers in the School of Health and Rehabilitation Sciences at Indiana University-Purdue University Indianapolis to study the effects of exercise on health conditions affecting millions of Americans.

Keith Avin, assistant professor of physical therapy, received a $674,186 grant to study the effects of aerobic and resistance exercise and myostatin inhibition on the prevention or reduction of skeletal muscle loss in animals with chronic kidney disease.

The study’s findings could advance efforts to help many of the 20 million Americans with chronic kidney disease suffering muscle loss, muscle weakness and reduced mobility.

“Chronic kidney disease is considered an accelerated aging model,” Avin said. “If you compare someone who is 50 years old and has end-stage renal disease, their muscles look like those of an 80-year-old.”

There is little known about the mechanism behind skeletal muscle loss associated with chronic kidney disease or what exercise can do to help patients with that disease improve the condition of their muscles. Avin’s study is designed to shed light on the latter.

“The goal is to see if exercise can mitigate the progression of the disease, providing prevention and treatment along the continuum of care,” Avin said.

One of the aims of the study is to compare the effects of high-intensity versus low-intensity exercise to see if they are different, he said.

“A lot of people see exercise as just something you do, and the more you do, the better,” Avin said. But with exercise, like any other drug, dosage matters: ”If we’re already looking at a system under stress, as is the case with someone with chronic kidney disease, and we tell patients to engage in high-intensity exercise, we may be doing more harm than good,” he said.

Avin will determine what dose of exercise is best for the study animals as a prelude to determining correct exercise dosages for humans.

The study will also examine whether exercise or drugs influence myostatin levels in patients with chronic kidney disease. Myostatin is a natural protein produced within the body that inhibits muscle growth.

Myostatin levels often go up in older people and in those with a disease, Avin said. The researchers want to see if exercise, which has previously been shown to influence myostatin levels, or a drug can reduce myostatin levels and have a beneficial effect on muscle.

For a different study, William Thompson, assistant professor of physical therapy, received a $462,400 grant to examine how exercise directs bone marrow stem cells to become bone cells and prevents them from developing into fat cells, thereby strengthening bones and offsetting the deleterious effects of conditions such as osteoporosis.

Stem cells in bone marrow are able to become several different types of cells, including bone cells or fat cells, Thompson said.

“There are a lot of cues that direct the fate of these stem cells, helping them decide what type of cell they will eventually become,” he said. “One of those cues is mechanical loading, which is the force exerted through your body during exercise. Such forces promote bone formation.”

What the cells eventually become is important, because fat cells don’t contribute to the strength of bones while bone cells do, Thompson said.

“The big picture is to understand how mechanical loading during exercise helps direct more of these cells to become bone cells and fewer to become fat cells,” he said. “When people get up and move, it helps bias those cells, providing the necessary mechanical cues to say, all right, I need to turn into a bone cell and not into a fat cell.”

These studies are being conducted in collaboration with Dr. Janet Rubin, a professor of endocrinology at the University of North Carolina School of Medicine, as well as Fred Pavalko, a professor of cellular and integrative physiology at the Indiana University School of Medicine.

The work will examine how molecules within these stem cells move within the cell to get where they need to be to turn mechanical force signals into biochemical responses, thereby promoting bone formation, Thompson said. 

“Our goal is to understand which molecules are involved in this process, which would then enable the design of exercise or pharmacological interventions to target these pathways,” he said. “Once you identify the targets, it’s possible to select which exercise regimens would be best to initiate intercellular signaling cascades to elicit anabolic responses.”