Published on August 11, 2026, a new review in the journal Neuroprotection shows that physical activity stimulates the release of molecules called exerkines, which travel through the bloodstream to reduce inflammation, protect nerve cells, and support brain function
The Muscle-Brain Connection in Parkinson’s Disease
A review published in the journal Neuroprotection argues that exercise does more than improve strength, balance, and mobility. It also stimulates the release of molecules known as exerkines, which travel through the bloodstream and may reduce inflammation, protect nerve cells, and support brain function.
That raises new questions about whether health systems should place greater emphasis on physical activity as part of routine neurological care. Parkinson’s disease affects more than 10 million people worldwide, and its prevalence is expected to continue rising as populations age.
“We found that the exerkines act as a medium for the crosstalk between the muscle and the brain,” said Salomón Páez-García, the author of the study. “Though the brain controls muscles, exercising muscles send beneficial signals back to the brain through exerkines.”
Salomón Páez-García, author of the study
Cellular Repair Mechanisms and Aging Muscles
Researchers have also uncovered a key reason why exercise is so effective at helping older muscles stay strong. A new study from Duke-NUS Medical School shows that physical activity can restore natural repair systems that weaken with age, helping muscles recover and maintain function later in life. The research team worked with collaborators from Singapore General Hospital and Cardiff University, publishing their findings in the Proceedings of the National Academy of Sciences.
Healthy muscles play important roles in metabolism, blood sugar regulation, and overall health. Beginning in middle age, muscle strength and function gradually decline, increasing the risk of falls, fractures, and slower recovery after illness or injury. One of the key regulators of muscle health is a growth pathway called mTORC1, which helps control protein production and muscle maintenance. In aging muscles, this pathway can become excessively active, causing muscles to focus more on building new proteins while becoming less efficient at removing damaged ones.
The researchers identified a gene called DEAF1 as an important factor behind this process. According to the study, DEAF1 levels rise in aging muscles, driving mTORC1 activity higher and disrupting the normal balance between protein production and protein removal.
Photo: sciencedaily.com
Under normal conditions, DEAF1 is regulated by a group of proteins known as FOXOs, but FOXO activity naturally declines with age. As a result, DEAF1 is no longer kept under tight control. To test their findings, the research team conducted experiments in both fruit flies and older mice. Raising DEAF1 levels caused muscles to weaken more rapidly, while lowering DEAF1 restored healthier protein balance and improved muscle strength.
How Physical Activity Resets Biological Pathways
The team discovered that exercise can help reverse this imbalance, provided the underlying regulatory system remains responsive. Assistant Professor Tang Hong-Wen from the Cancer and Stem Cell Biology Program at Duke-NUS served as the study’s lead author.
Photo: Euronews
“Exercise can reverse this process, correcting the imbalance. Physical activity activates certain proteins which lower DEAF1 levels, bringing the growth pathway back into balance. This allows aging muscles to clear out damaged proteins, rebuild themselves properly, and help them stay stronger and more resilient.”
Neuroplasticity & Parkinson’s: Why Exercise is Essential for PD Treatment
Tang Hong-Wen, Assistant Professor at Duke-NUS
While researchers caution that much of the evidence remains preclinical, the findings point towards a growing understanding of how skeletal muscle communicates with the brain. Existing medicines largely focus on controlling symptoms rather than slowing the underlying disease process, making lifestyle interventions an increasingly important area of research.
The findings reinforce calls from patient groups for exercise to be treated as a core component of Parkinson’s care rather than an optional extra. Although neurologists already recommend physical activity, dedicated rehabilitation services are often limited by workforce shortages and funding pressures.
“Exerkines are emerging as potential biomarkers and mediators of exercise-driven neuroprotection, but further high-quality studies are needed.”
researchers
Large clinical trials are still needed to determine whether targeting these pathways can alter the course of Parkinson’s disease in people.
