Stress is an upcoming problem that will surely get attention in the future. A lot more people in the world are experiencing some kind of physical or mental stress. People don’t know how to react with any threat or danger, ending up in severe stress. However, it is one of the body’s natural defense, and it makes the body flood with hormones to evade the threat. But prolonged exposure to stress can lead to severe mental disturbance, increase aging and chronic diseases, and also shorten the lifespan.
The molecular underpinning is still poorly understood. Recently, a scientist team at MDI Biological Laboratory in Bar Harbor studied the mechanism and hinted us a path. They used zebrafish to demonstrate the possible action of cortisol on the gene regulatory pathway. Cortisol, a stress hormone, secreted by the adrenal gland as a result of a stressful situation. It has got various effects on every metabolism of carbs, protein, and fat.
Prolonged stress can elevate cortisol levels in the blood by increasing the ACTH hormone. When too much cortisol is available, it will make the cell to become resistant to it, thereby resulting in poor anti-inflammatory property, and also dysregulated immune response. The underlying mechanism is through the activation of the glucocorticoid receptor (GR), which is a transcriptional regulatory protein. Also, it enhances inflammation by downregulating the kfl9 gene, another transcriptional regulator.
Krueppel-like factor 9, a protein encoded by a gene klf9. It is a key transcriptional regulator for cell proliferation, differentiation, and also plays a role in reactive oxygen species. Overexpression of the gene sensitizes the cell to oxidative stress. The researches believe that this is a key gene for understanding the optimal regulation of inflammation, and it is compromised during early-life stress.
As in the current situation COVID-19, we face a lot of stress in the hospital, home due to the isolation of people. The study suggests that the klf9 gene is responsible for controlling the physiological cortisol level. And when it exceeds the level, it upregulates the inflammatory system instead of reducing it.
They have researched with zebrafish as it shares the stress response with humans, and it is relatively economical. When zebrafish larva treated with cortisol for the first five days of life, they showed increased proinflammatory gene activity. Also, the scientist used the term inflammaging due to the overexpressed tlf9 gene, which might increase aging and age-related diseases.
The tlf9 gene may also responsible for regeneration because it usually depends upon the immune system. So, it might explain the link between defective healing property and chronic stress. There are many still unknown pathways of the tlf9 gene, which has to be studied. By underpinning every mechanism, we could develop a treatment for aging and age-related disease, possibly.
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Source: Medical Xpress