Scientists are discovering that chronic stress can alter gene expression, and consequently "stress", or our body’s response to it, can be passed down through generations as an unwanted legacy from our predecessors.

New research shows that chronic stress changes gene activity in immune cells before they reach the bloodstream. With these changes, the cells are primed to fight an infection or trauma that doesn’t actually exist, leading to an overabundance of the inflammation that is linked to many health problems. This is not just any stress, but repeated stress that triggers the sympathetic nervous system, commonly known as the fight-or-flight response, and stimulates the production of new blood cells. While this response is important for survival, prolonged activation over an extended period of time can have negative effects on health.

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 that’s going to be pro-inflammatory.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 findings suggest that drugs acting on the central nervous system to treat mood disorders might be supplemented with medications targeting other parts of the body to protect health in the context of chronic social stress.

Steven Cole, a professor of medicine and a member of the Cousins Center for Psychoneuroimmunology at UCLA, is a co-corresponding author of the study. The research is published in a recent issue of the journal Proceedings of the National Academy of Sciences.
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.

Another study just published in Biological Psychiatry found a similar connection between psychology and biology. People who had experienced severe stress during their lifetimes, such as survivors of the Holocaust, were found to have transmitted their biological stress response to their descendants.

"The notion that biological traits that are not coded by the sequence of DNA can be transmitted across generations is the focus of a field of research called epigenetics. This new paper implicates epigenetic regulation of a well-studied contributor to stress response, CRF1, in the intergenerational transmission of patterns of stress response," said Dr. John Krystal, Editor of Biological Psychiatry.

The study was led by Dr. Inna Gaisler-Salomon at the University of Haifa in Israel, and used adolescent rats that were subjected to stressful situations before mating. Previous studies in both humans and animals have shown that females exposed to stress before they conceive can pass on the effects to their children and grandchildren, who display increased brain CRF1 expression.

"It seems that CRF1 is a marker molecule that tracks the stress experience across generations, perhaps via the germline, and maternal care is minimally involved in this particular effect," explained Gaisler-Salomon.
CRF1 was elevated in the adult female progeny of stressed mothers, but was only activated if the offspring themselves encountered stress, indicating that CRF1 expression relies on a complex blend of the mother’s stress experiences in conjunction with the stress experiences and gender of their young .

"So why is this important?" asked Gaisler-Salomon. "Traditionally, it was believed that only genetic information is transferred from generation to generation via eggs and sperm cells. This study contributes to the notion that soft-wired information that is not written into the genetic code can also be transferred from one generation to the next via the germline".

How profoundly do these significant ‘genetic memories’ affect each of us, and how many of our responses are already pre-determined by the choices of our ancestors and predecessors? How far into our genetic futures does this legacy extend? Perhaps, as indicated in Exodus 34:7 of the Old Testament, "the iniquity of the fathers [is visited] on the children and the children’s children, to the third and the fourth generation."

Suddenly "The Sins of the Fathers (or Mothers)" takes on a wholly new, and scientific, meaning.

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