Epigenetics of physical exercise
Factors such as diet, exposure to environmental toxins, and stress have all been shown to play a role in affecting epigenetic modifications, especially by influencing methylation patterns in the DNA.
[27] Environmental conditions, such as eustress, strongly induces expression of the tumor suppressor TP53 gene by influencing epigenetic modifications to be made to the cancer cells genome.
Notably, a study found that mice exposed to short-term running phases had increased non-coding RNA transcription at telomeres as compared to sedentary controls.
In addition to restructuring the muscular and skeletal system to better handle mechanical stress, physical exercise also affects gene expression with respect to metabolism.
A bout of exercise increases c-miR-223 levels in the circulation in young healthy men, while lack of miR-223 leads to hippocampal-dependent memory deficits and neuronal cell death.
Likely arising from different mechanisms, both acute exercise and chronic endurance training have been shown to robustly modify the miRNA signature of human plasma.
More recently, it has been shown that conditional knockout of miR-132/212 gene cluster impairs memory and promotes gross alterations in hippocampal transcriptional profile in mice.
Overall miR-132 is one of the most studied miRNAs in the context of exercise and is proven to be instrumental in multiple functions in the brain, including neuronal development, synaptic plasticity and memory formation.
MiR-1, miR-133a, and miR-206 cluster levels were significantly elevated after exercise and correlated with performance parameters such as maximum oxygen uptake and anaerobic lactate threshold.
[49] Lastly, in a study conducted in 2018, the gene SOCS3, a cytokine signaling suppressor, was found to be upregulated in obesity and was shown to induce leptin and insulin resistance.
In addition, recent studies found that SOCS3 expression regulates energy and glucose homeostasis in several metabolic conditions, such as pregnancy, caloric restriction, and refeeding".
However, it’s been made clear that physical exercise is implicated in certain factors (BMI, metabolic rate, waist circumference) that are the parameters for diagnosing obesity.
[53][54] Studies have found that physical exercise is a viable, non-pharmaceutical approach to resisting and even undoing the harmful processes that cause sudden abnormal changes in brain cell activity resulting in seizures that characterize epilepsy.
[55] However, animal models have shown that epileptic patients undergoing physical exercise, especially if it's routine, develop more consistent BDNF levels similar to those unafflicted by the disorder.
[55] This return to normal-like BDNF fluctuations not only promotes generally healthier brain functioning but also reduced the total number of seizures experienced by the treated patients.
Physical exercise patients undergoing a high-intensity workout showed a notable increase in ROS that could significantly counter the benefits of moderate BDNF levels discussed prior.
[55] However, the detrimental effects of high intensity of workouts significantly diminish over time as the person naturally adapts to the oxidative stress that promotes ROS.
Studies have shown that subjects manipulated to experience chronic epilepsy showed a significant reduction of granule cells in the dentate gyrus, a subsection of the hippocampus critical to neurogenesis.
[52] Those same studies then demonstrated how subjects treated with physical exercise showed a return to normal-like granule cell count consequently improving neurogenesis and brain functioning.
Physical exercise has demonstrated to have positive effects on the epigenetic modulation of BDNF levels and neurogenesis maintenance specifically in epileptic patients.
[55] Alzheimer's disease(AD) is characterized by significant decline in cognition and memory with evidence showing that physical exercise can slow its progression and even provide return of loss function(s) in some cases.
[57] One of the primary modes of AD is the loss or atypical functionality of microglia and astrocytes caused by excessive build-up of amyloid beta peptide plaque upon the brain.
[57] The amyloid beta plaque causes the microglia and astrocytes regulatory components to be improperly activated resulting in excessive and inaccurate immune response that targets healthy neurons.
Studies have shown, in animal models and human patients alike, that consistent exercise inhibited the improper microglial activation mentioned previously through the production of certain myokines.
[53] A number of patients afflicted by neurodegenerative diseases like AD have notably lower counts of IL-6 which could explain higher instances of dysfunctional inflammatory response.
[57] Physical exercise can play a critical role in regulating inflammatory pathways through the epigenetic modulation of myokine IL-6 and BDNF in AD patients.
[57][58] Patients afflicted with schizophrenia show a drastic increase in microglial activation and arachidonic acid signaling, both major inflammation contributors which are known to cause neuronal loss and reduced function.
[58] As discussed previously, consistent exercise produces greater amounts of myokine IL-6 which regulates inflammatory pathways and increases production of IL-10, a cytokine that inhibits microglial activation.
[62] The key point being that consistent exercise over a substantial period of time results in a significantly lower baseline cortisol levels despite the short-term spikes caused by performing the activity.
Recent studies suggest that schizophrenia patients can benefit from long-term exercise which causes decreased neuroinflammation and basal cortisol levels associated with psychotic events.
