Epigenetics: Can Stress Influence Your Genes?



 
Epigenetics: Can Stress Influence Your Genes?

By Salimot Ojerinde, Geisinger Commonwealth School of Medicine, MBS 2018
Mentor: Dr. Gregory Shanower, PhD

Is there a long-term biological effect associated with severe stress, personal loss, and adverse conditions? In 2015, Rachel Yehuda and her colleagues at Mount Sinai published the results of their study examining the genes of 32 Jewish men and women that survived the Holocaust along with genes of 22 children who were born to these Holocaust survivors after the Second World War. Previous studies had indicated that children of Holocaust survivors have a higher risk of developing post-traumatic stress disorder, depression and anxiety, especially if the parents themselves have PTSD (Trappler et al, 2007), but there was no explanation as to how this could be possible. Yehuda’s research suggested that a genetic cause was responsible for this unusual inheritance of trauma. They found chemical changes in DNA of Holocaust survivors that were passed on to their progeny, suggesting that traumatic experiences affect DNA heredity in ways that can be passed on to children and grandchildren, a kind of “molecular scars”.

The phenomena that Yehuda and her team described is referred to as epigenetic inheritance. What is epigenetic inheritance, you ask? Before I can explain what epigenetics is, we need to understand the structure of DNA. Of the 50 trillion or so cells in the human body, each one contains about two meters of DNA (Science Focus, 2011). In order to fit the entire human genome into the cell nucleus, DNA is wrapped around clusters of proteins called histones forming a nucleoprotein conglomerate known as chromatin (Nature Education, 2014). Chromatin acts to organize the human genome within the nucleus. The functional units of DNA are genes that tell the cell what to do and what to become (Nature Education, 2014). Epigenetics involves chemical modifications to DNA and chromatin, which regulate whether or not genes are on or off depending on the environment or developmental circumstances. DNA methylation, for example, is associated with turning genes off during development and during normal cell metabolism. Some epigenetic marks such as histone methylation can help condense chromatin, preventing the cell from being able to read the genes, and essentially turning “off” the genes. Other epigenetic marks such as histone acetylation can help loosen the chromatin, making the genes easily accessible to the cell and the genes are turned “on”.

Epigenetic modifications occur in cells during development, as part of normal metabolism, and in response to different environmental conditions (both intracellular and extracellular in origin). Interestingly, when you were first conceived and your cells were becoming more specialized, your chromatin is thought to be a “blank slate”. This means that there are no epigenetic marks on it. It is only as embryonic cells began to divide and receive signals and information from surrounding cells that the epigenetic marks began to accumulate. It is during this time that epigenetic marks can be influenced by the environment outside of the developing embryo. The stressors that the mother endures during pregnancy can be transmitted through her blood stream to her developing fetus influencing the epigenetic state of the developing embryo.

So, to answer the question that was initially posed, “Is there a long-term biological effect associated with severe stress, personal stress, and adverse conditions?”, the answer, is well, possibly. A strong body of evidence suggests that epigenetic marks can have impactful consequences on the health of an individual which could subsequently impact the health and well-being of their future progeny. This can be observed in the case of the holocaust survivors, there is now evidence suggesting that the severe treatment they faced epigenetically changed a number of their genes. These changes were subsequently passed onto the progeny long after the stressor had been removed from the parents. What is also intriguing about this is that epigenetic modifications are thought to be completely removed in the developing human germline. So how were these epigenetic changes passed on the progeny? This is an area of research that is still being studied. Something is making it through this barrier, and that thing is DNA methylation and histone modifications.

 Watch this animation on the subject: https://www.powtoon.com/c/e06nXQvlMoT/1/m . 





References

Nature Education. (2014). Histone/Histones. https://www.nature.com/scitable/definition/histone-histones-57

Science Focus. (2011). How Long is Your DNA?.  http://www.sciencefocus.com/qa/how-long-your-dna

Trappler, Brian & Cohen, Carl & Tulloo, Rajeshree. (2007). Impact of Early Lifetime Trauma in Later Life: Depression Among Holocaust Survivors 60 Years After the Liberation of Auschwitz. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry. 15. 79-83. 10.1097/01.JGP.0000229768.21406.a7.

Yehuda R, Daskalakis NP, Bierer LM, Bader HN, Klengel T, Holsboer F, Binder EB.Biol Psychiatry. 2016 Sep 01; 80(5):372-80

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