Baylor Exercise Physiologists are Eliminating “Zombie Cells” to Improve Muscle Health After Chemotherapy
“Our ultimate goal is to translate our findings to a clinical population and help those that are sick and suffering return to a normal life.”
Cory Dungan, PhD, and Michael Wiggs, PhD, Assistant Professors in the Department of Health, Human Performance, and Recreation in Baylor University’s Robbins College of Health and Human Sciences, have received a $355,600 National Institutes of Health (NIH) Exploratory/Developmental Research Grant Award (R21) to study the impact that eliminating certain “zombie cells” can have on the muscle health of cancer patients who have received chemotherapy treatment.
“We are very excited for Dr. Dungan and Dr. Wiggs and the funding they have received to support their research,” said Dale Connally, PhD, Professor and Chair of the Department of Health, Human Performance, and Recreation. “Our Baylor exercise physiologists are doing exceptional and unique work around cancer and chronic diseases. This project helps blaze the trail for collaborative research that will translate interventions to human models.”
Skeletal muscle mass and function are key factors influencing an individual’s healthspan (the length of time that a person is healthy) and are closely connected to both physical and metabolic health. For cancer survivors in particular, the loss of muscle mass that occurs following cancer (called “cancer cachexia”) is a major contributor to mortality, as well as reduced quality of life after the disease.
Unfortunately, chemotherapy—one of the most extensively used treatments for cancer patients—is also associated with a loss of muscle mass. Chemotherapy treatments such as cisplatin induce DNA damage, further intensifying the harm to tissues and cells. Thus, even though they may be receiving an effective cancer treatment, patients undergoing chemotherapy can still experience severe muscle atrophy due to the treatment itself.
“Tens of thousands of Americans receive chemotherapy each year in hopes of curing them from cancer, with the goal of returning to a cancer-free normal life,” Dungan said. “One negative effect of chemotherapy is a loss of muscle mass and function, which can be mitigated by exercise training, but preclinical data suggest that the response to exercise is blunted following chemotherapy treatment—which could delay a cancer survivors return to a normal life.”
“It is well established that chemotherapy can significantly impair muscle function, leading to weakness and a reduced quality of life in cancer survivors,” Wiggs added. “Preserving muscle mass is crucial for overall health and well-being. While exercise is often recommended to mitigate muscle loss, chemotherapy's long-lasting effects can limit its effectiveness.”
This is where Dungan and Wiggs’s new research comes in. Recent work by their lab has focused on the accumulation of senescent cells—or, cells that have aged but not died—in muscle in response to the chemotherapy treatment cisplatin. These “zombie cells” have been linked to sarcopenia—muscle loss that occurs with aging—and are believed by Dungan and Wiggs to also be a contributing factor to the loss of muscle mass and function caused by chemotherapy. If senescent cells can be eliminated, muscle growth and regeneration may be improved.
In their newly-funded research, Dungan and Wiggs will explore whether receiving senolytics— a class of drugs that clear senescent cells—could benefit cancer patients receiving chemotherapy treatment by reducing atrophy and strengthening their response to exercise. By furthering their understanding of the mechanisms behind cachexia, as well as its treatment, Dungan and Wiggs are hoping to uncover new, creative therapeutic avenues to help preserve or restore muscle health and improve quality of life.
“Baylor's investment in cancer research has played a pivotal role in increasing patient survival rates, which now creates the challenge of identifying ways to improve the overall health of survivors,” Wiggs shared. “As exercise physiologists, we believe in using exercise as medicine for cancer patients. Importantly, this project aims at maximizing the benefits of exercise on skeletal muscle for survivors.”
Reflecting on the inspiration for and potential impact of their research, Dungan points to Matthew 10:8 and Jesus’s call to heal the sick.
“Our ultimate goal is to translate our findings to a clinical population and help those that are sick and suffering return to a normal life.”