Research Impact Story:
Brian Clark, PhD
Prevention and treatment of age-related muscle weakness and bone fractures.
The mission of the Osteopathic Heritage Foundation (the Foundation) is to improve the health and quality of life in the community through education, research and service consistent with our osteopathic heritage. To advance this mission, the Foundation has prioritized investments in scientific research and professional development at leading colleges of osteopathic medicine with the goal of advancing scientific discoveries, healthcare and delivery of patient care.
To this end, the Foundation has made significant investments in the Ohio University Heritage College of Osteopathic Medicine’s (Heritage College’s) research enterprise and the college’s contributions to advancements in patient care. One such investment is the Osteopathic Heritage Foundation Endowed Research Chair – in Honor of Harold E. Clybourne, DO, established in 2016. Dr. Clybourne was an orthopedic surgeon and one of the founders of Doctors Hospital in Columbus, Ohio. A 1923 graduate of Des Moines College of Osteopathic Medicine, Dr. Clybourne was a committed educator and established the Doctors Hospital orthopedic residency program in the early 1940’s, one of only four in the nation at the time. Dr. Clybourne remained engaged with Doctors Hospital until his death in 1969.
Brian Clark, PhD was named the Harold Clybourne, DO Endowed Research Chair in 2016. Dr. Clark is a professor of physiology and neuroscience in the Department of Biomedical Sciences at Ohio University and has served as the Executive Director of the Ohio Musculoskeletal and Neurological Institute (OMNI) since 2008. Under Dr. Clark’s leadership, Ohio University and OMNI have become one of the top sites in the nation for early phase clinical trials investigating new treatments for sarcopenia. Sarcopenia is a muscle disease prevalent in older adults and is characterized by low muscle strength, poor muscle quality and reduced muscle mass. Dr. Clark’s research focuses on developing effective interventions to improve muscle function and mobility in older adults and patients with orthopedic and neurologic disabilities. He has authored more than 180 articles and book chapters including several of the most cited articles in the field. Numerous private industry sponsors support his work, and he has received multiple grants from the National Institutes of Health (NIH), including numerous prestigious RO1 awards reserved for mature research projects with strong preliminary data supporting the hypothesis. In total, more than $30 million in grant funding has supported his work.
Dr. Clark earned his undergraduate degree in biology from Western Carolina University. He received a master’s degree in exercise physiology, a certificate of advanced study in gerontology, and a Doctor of Philosophy degree in neuromuscular physiology from Syracuse University where he was named the doctoral student of the year. He joined Ohio University in 2006 as an Assistant Professor, was promoted to Associate Professor in 2011 and then Full Professor in 2012. He was selected as an Ohio University Presidential Research Scholar in 2018.
Dr. Brian Clark studies the role of the nervous system in muscle health.
Investing in the Future of Patient Care
Dr. Clark is an internationally recognized expert in aging and muscle health and his research has changed the way scientists study – and physicians treat – age-related muscle weakness and osteoporosis. His focus on helping people live healthy lives and disease prevention is central to the principles and practice of osteopathic medicine.
Cheryl Graffagnino, Program Officer
Advancing understanding of the root causes of age-related muscle weakness and bone fractures and supporting development of targeted treatment and prevention strategies.
The Future of Patient Care:
Helping people live independently longer through the prevention and treatment of muscle weakness and osteoporosis-related bone fractures.
Dr. Clark spoke with Osteopathic Heritage Foundation staff about his research and the impacts of the Foundation’s investments.
What is your area of research?
My research focuses on understanding why we lose muscle strength and function as we age and how it can be prevented. Everyone experiences changes in muscle function as they age, however, some people experience severe changes limiting mobility and their quality of life. Our research focuses on understanding why some people fare worse than others as they age and ways to prolong the “healthspan” – the period in life when one is healthy and free from serious disease.
Three factors contribute to decline of muscle strength and function – muscle mass, muscle quality and the nervous system. We study how these factors, independently and together, contribute to loss of muscle strength and function as we age. I am particularly interested in the role of the nervous system, including the brain, nerves and skeletal muscles, in age-related health and disease.
What is the role of the nervous system in muscle health?
Until the early 2000s, it was believed the primary reason people experience muscle weakness and lose strength as they age is because they lose muscle mass. This seemed logical as muscle size noticeably decreases as people age.
However, in our studies of healthy, young adults who were voluntarily immobilized for several weeks, we observed significant declines in muscle strength not explained by loss of muscle mass. Instead, we found these declines were caused by a disruption in the signals from the brain responsible for making muscles contract. We then evaluated this in older adults and found similar disruptions in the signals from the brain to the muscles, affirming the nervous system also contributes to declines in strength. Our findings demonstrated loss of muscle mass is not the sole reason people lose strength as they age and changed the paradigm of research in the field.
Why is it important to study the effects of aging on muscle health?
Muscle weakness in adults over the age of 75 is a better predictor of death than high blood pressure. Loss of muscle strength puts older adults at a four-times greater risk for mobility limitations, affecting their ability to carry out everyday functions like climbing stairs, carrying groceries or cleaning. These factors also affect an older adult’s ability to live independently and put older adults at greater risk for falls, which can have devastating consequences. Preserving muscle health is a means to enhance quality of life for aging adults.
By 2034, it is predicted the number of people in the U.S. over the age of 65 will be greater than the number of people under the age of 18. Our society is aging and the financial and human costs of caregiving for the older population who cannot live independently will reach a crisis.
Understanding how declines in muscle mass and nervous system signaling each contribute to loss of muscle function and weakness allows the development of more precise recommendations and targeted treatments. It supports personalized strategies to maximize a person’s ability to maintain muscle strength and function as they age.
What scientific discoveries have been made by the Clark lab?
Our most important discoveries are related to the changes in the nervous system as we age and the impact those changes have on muscle health. We have demonstrated the readiness of a cell to respond to a stimulus (neural excitability) is reduced in older adults with muscle weakness. Our current research focuses on deciphering how the brain and nervous system send messages to the cell and how these messages impact cellular and muscular activities. This research is fundamentally changing the way healthcare providers are diagnosing and treating muscle weakness, especially in older adults. If these complex pathways are better understood, medications and treatments targeting the nervous system and addressing underlying causes of muscle weakness can be developed.
Our research in the field of osteoporosis, an age-related degeneration of bone tissue, has led to an innovative diagnostic approach. Currently, bone health is assessed using dual-energy x-ray absorptiometry (DEXA), which evaluates the density (how tightly packed something is) of bone based on its chemical composition. While low bone density indicates osteoporosis, it does not predict whether a person will experience a fracture. However, there is a compelling reason to think whole bone strength would be an exceptional predictor of fracture. Our team at OMNI developed a prototype device called Cortical Bone Mechanics Technology. We formed a MedTech start-up company (OsteoDx Inc.) working to commercialize this device. This technology uses vibration analysis techniques to estimate bone strength, which we hope could have clinical utility and improve the way we assess a patient’s risk for experiencing an osteoporosis related fracture. We have received investment funding and small business innovation research funding from the NIH to help us prepare the OsteoDx technology for use in patient care. OsteoDx was recognized as the “Most Innovative Technology” by NASA ITech Ohio in 2020 and was named one of the top 20 university-based start-ups in 2019.
We are also leading global efforts to establish a consistent definition and standardized approaches for the diagnosis and treatment of sarcopenia. Because our research has challenged the notion of muscle loss as the defining characteristic of sarcopenia and emphasizes the importance of muscle weakness in adverse health outcomes, we are advocating for diagnostic criteria prioritizing muscle weakness as the defining characteristic of the disease.
How has the Osteopathic Heritage Foundation’s funding investment helped you impact patient care?
The Foundation’s funding was instrumental in supporting the early research needed to position our lab to secure NIH funding. However, NIH funding can only be spent on the specific project for which it was granted, meaning alternative sources of funding are needed to develop new ideas and innovations. The Foundation’s funding allows us to pursue new research ideas and improve patient care. For example, we were able to use Foundation support to procure new technology to help our lab improve methods for data collection in test subjects. The new technology made it easier to recruit test subjects for studies and collect preliminary data that led to a $3.5 million funding award from the NIH to support further research.
How does conducting your research at a College of Osteopathic Medicine and the osteopathic profession’s focus on treating the whole person influence your work?
I was drawn to the Heritage College because of its whole-person approach. This resonated with my personal philosophy and background in exercise and integrative physiology, both of which take a holistic approach to health. The investigation of aging systems and geriatrics inherently involves studying the body as a cohesive system to comprehend the underlying factors behind the biology and problems associated with aging.
What is next for your research?
Our research in osteoporosis is striving to bring OsteoDx’s technology to patient care to improve diagnosis and treatment of osteoporosis. This will continue to be a priority. Osteoporosis is a significant medical issue in aging populations. One in two women and one in four men will have a bone break, significantly impacting their quality of life. Our work ultimately aims to better identify patients at high risk for fractures and tailor treatment and prevention strategies to improve quality of life and enable sustained independence for people as they age. There are still many studies to be conducted but this is our long-term goal.
Similarly, our work related to the diagnosis and treatment of sarcopenia will have important impacts on aging and health. Expanding knowledge and understanding of the factors contributing to muscle weakness in aging will also support the development of targeted treatments and prevention measures to keep people living independently for as long as possible. Weakness is what predicts poor function and outcomes for older adults. Determining a common definition for weakness and identifying the most effective measures are essential to developing treatment and prevention strategies.
Brian Clark, PhD
Professor of Physiology and Neuroscience, Department of Biomedical Sciences at Ohio University
Executive Director of the Ohio Musculoskeletal and Neurological Institute (OMNI)
Harold Clybourne, DO Endowed Research Chair and Professor
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