Home Therapeutic relationship Although the benefits of exercise may outweigh the risks, genetic status should be considered when recommending it as a therapy – ScienceDaily

Although the benefits of exercise may outweigh the risks, genetic status should be considered when recommending it as a therapy – ScienceDaily


Mitochondria are the primary source of energy production in our cells, and endurance exercise is generally known to improve mitochondrial function. However, the benefits of exercise in patients with primary mitochondrial diseases, which are heterogeneous and caused by various genetic mutations, were largely unknown.

In a new study, researchers at the Children’s Hospital of Philadelphia (CHOP) have demonstrated that the benefits of endurance exercise may vary depending on the type of mutation involved in mitochondrial disease, and although the benefits of exercise outweigh the risks, the mitochondrial genetic status of patients should be considered when recommending exercise as therapy. The results were published online today by the Proceedings of the National Academy of Sciences.

Primary mitochondrial diseases are the most common inherited metabolic disorders, affecting approximately 1 in 4,200 people. These disorders can be caused by hundreds of different mutations in nuclear DNA (DNA in our cells) or mitochondrial DNA (mtDNA , or the DNA in the mitochondria in our cells). Universal treatments for these patients are limited. However, endurance exercise has been shown to improve mitochondrial function in healthy people and reduce the risk of developing secondary metabolic disorders like diabetes or neurodegenerative disorders.

However, these recommendations were based on healthy people without primary mitochondrial disease. Therefore, the researchers wanted to determine the effectiveness for these patients and whether they actually benefited from endurance exercise.

“There was no consensus among clinicians who see patients with mitochondrial disease about whether endurance exercise really provides benefits,” said Patrick Schaefer, PhD, postdoctoral fellow at the Center for Mitochondrial Medicine and epigenomics of CHOP and first author of the study. “Exercise helps create more mitochondria, but if those mitochondria still have the mutations associated with primary mitochondrial disease, exercise may put some patients at risk.”

Due to the heterogeneity of primary mitochondrial disease among patients, researchers used animal models to study five disease-causing mutations. The aim of the study was to determine the relationship between mitochondrial mutations, the response to endurance exercise and the underlying molecular pathways in these models with distinct mitochondrial mutations.

The study found that endurance exercise had different impacts on patterns depending on the mutation involved. Exercise improved the response in the model with the mtDNA ND6 mutation in complex I. The model with a CO1 mutation affecting complex IV showed significantly fewer positive exercise-related effects, and the model with an ND5 complex 1 mutation did not respond to exercise at all. In the Ant1 nuclear DNA-deficient model, endurance exercise actually worsened cardiomyopathy.

Additionally, the researchers were able to correlate the gene expression profile of skeletal muscle and heart in the model with response to exercise and identified oxidative phosphorylation, amino acid metabolism, and cell cycle regulation as key pathways in response to exercise, suggesting how the model might be adapted. to study exercise responses in humans with primary mitochondrial disease.

Despite the mixed responses from the models used in this study, the authors note that the benefits of exercise outweigh the risks in most cases. However, the physical and mitochondrial state of the patient should be considered when recommending therapeutic exercises. Additionally, the study could help researchers identify biomarkers and pathways to help predict mitochondrial response to exercise in both mitochondrial patients and the healthy population harboring different mitochondrial haplogroups.

“This work is of fundamental importance in demonstrating that individuals with different mitochondrial bioenergetics will respond differently to endurance exercise,” said study lead author Douglas C. Wallace, PhD, director of the Center. of mitochondrial and epigenomic medicine from CHOP and Michael and Charles. Barnett Endowed Chair in Pediatric Mitochondrial Medicine and Metabolic Diseases. “This is of great relevance to individuals ranging from athletes to patients with mitochondrial disease, and everyone in between.”

This study was supported by the German Research Foundation through SCHA grant 2182/1-1, National Institutes of Health grants NS021328, MH108592, and OD010944, and US Department of Defense grants W81XWH16-1 -0401 and W81XWH-21-1-0128. Schematics were created with BioRender.com.