Wednesday, November 6, 2013

Chronic Stress Changes Your Genes

It's now known that chronic stress not only will damage your body, it actually changes your genes - and that is not good news for the millions of people world-wide who suffer in unremitting stressful situations nor for our health care system.

The stress reaction, also known as the fight or flight reaction, is something we all have.  While this response is important for survival, prolonged activation over an extended period of time has negative effects on health.

During a stress reaction, you experience an event, say an argument or near accident.  Your heart races, your palms sweat, and your body reacts to the sudden dumping of adrenaline into your bloodstream.  After time, the adrenaline is used up, and our body returns to normal.

With chronic stress, whatever is stressing you, say a demanding boss or a requirement to work long hours over a long period of time, your body continually pumps out adrenaline without an opportunity to recover.  The end result can be burnout or perhaps a wide variety of debilitating diseases from heart attack to stroke to Alzheimer's, to name but a few.

New research shows that chronic stress also changes the activity of the genes in your immune cells before they reach the bloodstream. These changes "instruct" cause the cells in your immune system to fight an infection or trauma that doesn't exist.  This leads to an overabundance of the inflammation linked to so many health problems.  One thing a hyped-up immune system may do is to attack your own body with an auto-immune disease such as arthritis.

A study in animals showed that this type of chronic stress changes the activation, or expression, of genes in immune cells before they are released from the bone marrow.
  • Genes that lead to inflammation are expressed at higher-than-normal levels,
  • while the activation of genes that might suppress inflammation is diminished.
Ohio State University scientists made this discovery in a study of mice. Their colleagues from other institutions, testing blood samples from humans living in poor socioeconomic conditions, found that similarly primed immune cells were present in these chronically stressed people as well.

"The cells share many of the same characteristics in terms of their response to stress," said John Sheridan, professor of oral biology in the College of Dentistry and associate director of Ohio State's Institute for Behavioral Medicine Research (IBMR), and co-lead author of the study. "There is a stress-induced alteration in the bone marrow in both our mouse model and in chronically stressed humans that selects for a cell to be pro-inflammatory.

"So what this suggests is that if you're working for a really bad boss over a long period of time, that experience may play out at the level of gene expression in your immune system."

The mind-body connection is well established, and research has confirmed that stress is associated with health problems. But the inner workings of that association -- exactly how stress can harm health -- are still under investigation.

Under normal conditions, the bone marrow of humans is making and releasing billions of red blood cells every day, as well as a variety of white blood cells that constitute the immune system. Sheridan and colleagues already knew from previous work that stress skews this process so that the white blood cells produced in the bone marrow are more inflammatory than normal upon their release -- as if they are ready to defend the body against an external threat.

A typical immune response to a pathogen or other foreign body requires some inflammation, which is generated with the help of immune cells. But when inflammation is excessive and has no protective or healing role, the condition can lead to an increased risk for cardiovascular diseases, diabetes and obesity, as well as other disorders.

In this work, the researchers compared cells circulating in the blood of mice that had experienced repeated social defeat to cells from control mice that were not stressed. The stressed mice had an average fourfold increase in the frequency of immune cells in their blood and spleen compared to the normal mice.

"This study provides a nice mechanism for how psychology impacts biology," said study first author Nicole Powell, a research scientist in oral biology at Ohio State. "Other studies have indicated that these cells are more inflammatory; our work shows that these cells are primed at the level of the gene, and it's directly due to the sympathetic nervous system."

This same pro-inflammatory immune-cell profile has been seen in research on parents of children with cancer.
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Story Source:  N. D. Powell, E. K. Sloan, M. T. Bailey, J. M. G. Arevalo, G. E. Miller, E. Chen, M. S. Kobor, B. F. Reader, J. F. Sheridan, S. W. Cole. Social stress up-regulates inflammatory gene expression in the leukocyte transcriptome via  -adrenergic induction of myelopoiesis. Proceedings of the National Academy of Sciences, 2013

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