Unveiling the Anti-Inflammatory Benefits of Exercise
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Like the stress response, Inflammation is a vital defense mechanism of the body, playing a crucial role in protecting against infections and injuries. However, when stress or inflammation become excessive and chronic, they can contribute to the development of various debilitating human diseases, including autoimmune disorders, cardiovascular diseases, diabetes, and cancer. These diseases make up the current epidemic of chronic noncontagious disease epidemic. As we have often discussed in my books and in the MGC newsletter, chronic activation of the immune system can also originate in the gut in response to diet-induced imbalances of the gut microbiome and the gut-based immune system.
The good news is that exercise, known for its numerous health benefits, has been found to modulate the immune system. A recent study by Murugathasan et al from York University in Toronto sheds light on the fascinating long-term effects of chronic moderate exercise on the inflammatory responses of macrophages, a group of immune cells which are a key component of the immune system.
“The good news is that exercise, known for its numerous health benefits, has been found to modulate the immune system.”
The study conducted on laboratory mice explored the effects of chronic moderate intensity training on a group of immune cells originating in the bone marrowy (bone marrow-derived macrophages or BMDMs). The researchers discovered that exercise induced persistent metabolic rewiring in these macrophages, leading to profound changes in their inflammatory responses. BMDMs from exercised mice exhibited a decreased activation of the NF-κB pathway (The transcription factor NF-κB regulates multiple aspects of innate and adaptive immune functions and serves as a pivotal mediator of inflammatory responses) and reduced expression of pro-inflammatory genes when exposed to lipopolysaccharide (LPS), a potent inflammatory stimulus derived from the membrane of bacteria. Additionally, the exercised mice showed an increase in the expression of genes associated with a subgroup of immune cells (M2-like macrophages), which have anti-inflammatory properties.
To unravel the mechanisms responsible for these observed changes, the researchers delved deeper in the biology of macrophages. They found that exercise improved mitochondrial quality in macrophages, increasing their reliance on oxidative phosphorylation, a more efficient energy-producing process that generates less harmful reactive oxygen species (ROS). Consequently, the exercised macrophages demonstrated a reduced production of mitochondrial ROS. Furthermore, the study employed a special type of analysis (ATAC-seq analysis) to investigate changes in the accessibility of genes associated with both inflammatory and metabolic pathways. The findings showed that exercise can affect the way certain parts of cells are accessed and used, indicating that changes in how genes are controlled by the environment during exercise can impact the way immune cells respond to inflammation.
“…exercise can affect the way certain parts of cells are accessed and used…”
This study offers valuable insights into the remarkable benefits of chronic moderate exercise in modulating the inflammatory responses of macrophages. By reprogramming macrophage metabolism and modifying their epigenetic landscape (the overall pattern of chemical markers and modifications on the DNA and histone proteins that help regulate gene expression without altering the underlying genetic code), exercise promotes an anti-inflammatory phenotype in these immune cells. The findings highlight exercise as a powerful immunomodulator that may help prevent or alleviate inflammatory diseases.
“By reprogramming macrophage metabolism and modifying their epigenetic landscape, exercise promotes an anti-inflammatory phenotype in these immune cells.”
While this study provides a significant foundation for understanding the link between exercise and macrophage function, there are still avenues for further exploration. Future research could investigate the precise signaling pathways and molecular mechanisms that mediate the observed metabolic and epigenetic changes. Additionally, while the results obtained in laboratory mice are fascinating, extending these investigations to human studies could provide valuable insights into the translational potential of exercise as a therapeutic and preventive strategy for combating chronic inflammation.
The study demonstrates that chronic moderate exercise has transformative effects on an important component of the immune system, resulting in dampened inflammatory responses. By enhancing mitochondrial quality, promoting oxidative phosphorylation, and altering chromatin accessibility (the degree to which the DNA within the chromatin structure is accessible and able to be transcribed by cellular machinery), exercise reprograms macrophages to adopt an anti-inflammatory phenotype. These findings deepen our understanding of the immunomodulatory benefits of exercise and underscore the importance of physical activity in maintaining a healthy immune system. Incorporating regular exercise into our lives may prove to be a powerful tool in preventing and managing chronic inflammatory diseases. This study has identified one of the mechanisms by which this simple therapeutic intervention works.
E. Dylan Mayer is a graduate from the University of Colorado at Boulder, with a major in Neuroscience and minor in Business. He is fascinated by the close interactions between nutrition, exercise and human health, especially with regard to the brain-gut-microbiome system. In order to expand his knowledge in this field, Dylan will complete his master’s degree in Human Nutrition from Columbia University in New York City in August 2023.