## Life experiences are reflected in the epigenome

In addition to the already mentioned, easily measurable factors that affect the human organism (type and amount of food, exposure to chemical substances, biological causes of aging), there are other factors influencing gene expression, but they are rather subjective and result from the individual's reaction to a particular situation. The influence of these factors, namely life experiences of a social nature, on the human epigenome is studied by a separate branch of the scientific discipline – behavioural epigenetics. One of the studies conducted in mice demonstrates that trauma experienced can be transmitted to at least the next two generations. The authors of this study used the olfactory (smell) sensation, which they associated with fear of pain (Figure 7.1). The volatile substance acetophenone, reminiscent of the smell of cherry blossoms, with the olfactory receptor Olfr151 responding to acetophenone. Males of the P0 (see Chapter 6 - How environment can affect our genes) were placed in an environment with the odour of acetophenone and, simultaneously with the activation of the sense of smell, received an electrical discharge in a limb that caused pain. After several repetitions, the males with this experience were crossed with a female that had not had this experience. When the offspring of the F1 and F2 generations were exposed to the odour of acetophenone, these individuals showed a high level of nervousness compared with the control group, although they never received an electric shock. Strikingly, even in the F2 generation, which had been created by artificial insemination and rearing by surrogate parents. This experiment served as evidence that sensitivity to acetophenone is a consequence of heredity and is transmitted based on the behaviour of the P0 generation. Evidence of reduced methylation of the Olfr151 receptor in the tested mice also confirmed that epigenetic transfer had occurred.

In examining human behavioural epigenetics, we must go back to the time of World War II. Part of this war was the so-called "Winter War" (1939-1940) and the "Continuation War" (1941-1944) between the Soviet Union and Finland. Using demographic data of Helsinki children born in 1934-1944, a study was conducted to determine whether wartime experiences could be transferred to the next generation, who did not experience the war. During the war, the government offered the voluntary opportunity to evacuate children from Finland to Denmark and Sweden to protect them from the horrors of war. Most children, with the average age of 4.6 years, were evacuated without a parent, with the average duration of separation from their parents was 1.7 years. Children of women who were evacuated as infants were found to have a twofold increased risk of developing one of the psychiatric diagnoses and a fourfold increased risk of developing bipolar disorder or depression compared with the control group. It is interesting to note, however, that psychiatric problems occurred only in the daughters of the evacuees and not in the sons. A similar association was also not observed in children of men who were evacuated in childhood. A negative impact on offspring was also found in the context of prison camps during the American Civil War around 1864. The study was based on the medical records of approximately 4,600 children of fathers interned in overcrowded camps with poor sanitation and inadequate nutrition, and on records of 15,300 children whose fathers were war veterans but not prisoners. Observation of these two groups revealed that the sons and grandsons of ex-captives had an 11% higher mortality rate due to cerebral haemorrhage and an increased risk of dying from cancer. Overall, this appeared to be more of a male line of inheritance, and the health of the daughters and granddaughters was not affected.

On September 11, 2001, there was a terrorist attack on the World Trade Centre in New York, known as the "Twin Towers". Two hijacked planes crashed into the Twin Towers, bringing down both towers. A group of 38 pregnant women who survived this terrorist attack participated in the research of Rachel Yehud, a professor of psychiatry and neuroscience who specialises in post-traumatic stress disorder. PTSD is an anxiety disorder that some people develop after experiencing an extremely stressful event. The triggers for this disorder can vary in severity depending on psychological resilience and experience, which is why not all 38 women developed it. Cortisol is a stress hormone whose level increases in a person in difficult situations, but in women it decreases rather than increases in PTSD. In addition, the expression profile of 17 other genes involved in immune response, nerve signalling, and brain function was altered. The researchers also measured the cortisol levels of the children born to these women. If the women were in their second or third trimester when the Twin Towers fell, the newborns also had lower cortisol levels. The exact explanation of the mechanism is still being studied, but it is more than certain that the traumatic event experienced by the mother during pregnancy had an impact on changing gene expression in the next generation. And because cortisol also plays a role in food metabolism, the offspring of people with PTSD are more sensitive to stress as food deprivation, and vice-versa, they have a higher risk of obesity in an environment where they have enough food.

Another phenomenon over which humans have little influence is the occurrence of natural disasters such as volcanic eruptions, earthquakes, tornadoes, floods, fires, or landslides. One of the studies that examines the effects of a natural disaster during pregnancy focuses on the ice storm that occurred in Quebec in 1998. This storm killed 28 people and injured 945. It was a 6-day period of freezing rain that formed layers of ice up to 11 cm thick on power lines and poles, leaving more than four million people without electricity, and in some places, it took a month to restore power. The 1998 ice storm is ranked as the costliest natural disaster in Canada's history, affecting more people than any other natural event in Canada. Women who were pregnant at the time underwent an assessment of the extent of suffering they experienced, both objectively and from their subjective perspective. The children born were examined for their DNA methylation levels at age 8 and then at age 15. Indeed, there was a change in methylation levels in 957 genes whose functions were mainly related to the immune system. This study showed that prenatal stress can affect the epigenome, with potentially long-lasting effects.