How Stress Permanently Changes Our Genes

We all know that run-down feeling that comes after a stressful work week, when you swear your boss is making you sick. New research shows that chronic stress can change your immune cells—and may actually cause an illness or disease.

Chronic stress can have negative effects on your health because it triggers the sympathetic nervous system. John Sheridan, associate director of Ohio State University's Institute for Behavioral Medicine Research, said that acute stress—caused by things like getting fired, moving, or losing a loved one—can cause a “fight or flight” response. Common chronic stressors include being in a bad marriage, being a caregiver, or working for a difficult boss.

“Oftentimes, chronic stress is chronic because there is no easy solution to the problem,” said Debora Kane, a Brooklyn-based therapist. “In the case of caring for a family member, child, or older parent who has acute or serious medical problems, there may not be a way to eliminate the stress endemic to the situation. Then we need to look for ways to alleviate stress.”

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How Stress Affects the Body

The Ohio State researchers studied mice and found that chronic stress changed the activation, or expression, of genes in their immune cells—before they even hit the bloodstream. Genes that produce inflammation were expressed at higher-than-normal levels, and genes that could alleviate inflammation were diminished. 

Sheridan subjected the mice to constant stress in order to mimic the persistent stressors experienced by humans. Male mice that lived together were interrupted by an aggressive male for two hours at a time, which triggered their fight or flight response as they were repeatedly defeated by the new mouse.

In both humans and animals, red and white blood cells are released from the bone marrow every day. Sheridan said that he already knew from previous research that stress causes white blood cells to be more inflammatory than normal—a mechanism that helps the body defend itself against a threat, such as a virus. Immune responses require inflammation, which immune cells help to produce. When inflammation is too high and has no healing role, it can boost a person’s risk for cardiovascular diseases, diabetes, and obesity, just to name a few.

Sheridan compared cells in mice subjected to the aggressive mouse to those that lived without interruption. The stressed mice had an average fourfold increase in the frequency of immune cells in their blood and spleens compared to the normal mice. In fact, a genome-wide evaluation of cells in the stressed mice showed nearly 3,000 genes expressed at different levels—higher and lower—in comparison to the non-stressed mice.

Many of the 1,142 up-regulated genes in the immune cells of the stressed mice allowed the cells to become inflammatory quickly, the researchers found.

“This study provides a nice mechanism for how psychology impacts biology. 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,” said Nicole Powell, a research scientist at Ohio State.

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Similar Findings in Humans

Steve Cole, a professor of medicine and a member of the Cousins Center for Psychoneuroimmunology at the University of California, Los Angeles, conducted similar research that was also published recently in Proceedings of the National Academy of Sciences.

Cole performed a statistical analysis of genome function to see how a person’s perception of his or her surroundings can affect their physical wellbeing. He studied genetic samples from Sheridan’s mice and from healthy humans with either low or high socioeconomic status.

The human analysis showed that 387 genes differed between low and high socioeconomic status adults, and that the up-regulated genes showed more inflammation. The scientists also noticed that about one-third of the genes found in the persistently stressed humans were also present in the stressed mice.

Cole said the research shows that experiencing a low-grade sense of uncertainty or threat over a long period of time could have significant effects on the body.

“Seemingly mundane factors, such as loneliness and socioeconomic disadvantage, that stretch out over long periods of time show stronger links to the activity of inflammation-related genes than do more ‘acute’ stressors,” Cole said. “Decades of exposure to this greater inflammatory signaling tends to ‘fertilize’ the progress of chronic diseases, such as heart disease, cancer, and neurodegenerative diseases.”

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