Isabelle Mansuy, your new book is entitled "Wir können unsere Gene steuern" (“We can control our genes”). That sounds promising yet adventurous at the same time. How can this be done?
Isabelle Mansuy: When I write that we can control our genes, I mean that we can influence how our genetic information is read and interpreted by our body: In other words, how our genes are switched on or off. How this can be done is the subject of epigenetic research. But we can’t change the genes themselves.
What can influence the activity of our genes?
Mansuy: Gene activity is constantly being modulated by the way in which we live – by factors such as our social environment, diet and exercise. And if we suffer any traumatic experiences, for example, they write themselves into our body and our epigenome.
What is the epigenome – and how does it stand in relation to the genome?
Mansuy: Genome and epigenome are complementary and mutually affect each other. The genome is the genetic code, the DNA – like the hard disc of a computer. The epigenome is responsible for the way in which this code is read. In a computer, this would be the software. The epigenetic mechanisms control how genetic information is interpreted. The genome is largely fixed. Although it can change, through mutations for example, the epigenome is much more dynamic than the genome. It is continuously being modulated – throughout our life, but also every moment, depending on what we are doing.
How does the epigenome control the expression of our genes?
Mansuy: That’s a cascade of reactions. All round our genetic code are epigenetic mechanisms which help to express this code, to interpret it. These are markers on the DNA – molecules and proteins that influence how genetic information is read.
You said that our epigenome is constantly being modulated, depending on how we live. How should we understand this?
Mansuy: Our environment affects our epigenetic markers in all kinds of different ways – through our diet, exercise, how we sleep, and our social environment. These influences can be positive or negative. Positive examples include a good social environment, a healthy diet and exercise. We’ve been able to demonstrate how important this is with experiments on mice kept in large cages with lots of options for exercise and play, and in groups in which they feel comfortable. We’ve seen that this environment changes the epigenetic markers in their brain, blood and also germ cells. These changes are also very stable.
What kind of things have a negative impact on the epigenome?
Mansuy: Traumatic experiences such as violence suffered in childhood, war traumata, the death of a parent, neglect, humiliation. This also applies to verbal violence inflicted by parents, for example. We are far too unaware that children in European countries, where there are no wars, are very often exposed to traumatic events too. One in four children suffers violence in the family, for example.
What are the consequences of such experiences?
Mansuy: Such a traumatic experience changes the epigenome and this in turn influences the activity of the genes.
This is how traumatic experiences are written into the body. This can trigger not only psychiatric problems such as anxiety or depression but also physical disorders such as heart problems, cancer, or autoimmune diseases. We’ve been able to demonstrate that traumatic experiences in the epigenome of the brain leads to permanent changes.
You’ve proven that these changes to the epigenome occur in mice. Can this be applied to humans?
Mansuy: We’ve found comparable epigenetic differences in men who suffered trauma in childhood as in mice.
One of your key statements is that epigenetic changes are passed on to future generations. How does this occur?
Mansuy: We know that certain markers of the epigenome are passed on at conception. The sperm passes on its DNA —and also the epigenetic markers that accompany it. The same applies to the egg cell. This means that both sides contribute a genome and epigenome, which are then recombined. However, we don’t yet know exactly what happens during the recombination of the epigenome. We don’t know exactly what is retained, what’s lost or what is possibly doubled.
There is no scientific consensus about whether epigenetic changes can be inherited. Do you have evidence?
Mansuy: Scientific experiments have been conducted in which ribonucleic acids (RNAs, copies of parts of the DNA) from the sperm of traumatized male mice were injected into egg cells. The offspring of these mice had the same symptoms from the traumata as the mice that had been directly exposed. This is the proof that RNA contains and passes on information from past experiences.
Doesn’t that contradict your statement that the epigenome is constantly evolving?
Mansuy: There are parts of the epigenome that are very stable and others that are highly dynamic. This explains why some genes have an epigenome that remains unchanged throughout a person’s life.
How can the changes in the epigenome be verified?
Mansuy: The epigenetic changes raise or lower the number of epigenetic markers that determine how DNA is read and used. These include DNA methylation, which causes a chemical modification to the cell’s building blocks – which doesn’t amount to a genetic mutation of the DNA but merely an epigenetic modification. Another marker is non-coding RNA, which can attach to the DNA. These factors can be verified in the person’s tissue, blood, saliva or sperm.
You write that epigenetic changes can be passed down to the grandchildren generation. Does it come to an abrupt stop there?
Mansuy: This we don’t know. In mice, we know that traumata symptoms can even be felt by the fifth generation. In humans, it’s been observed that war traumata symptoms can be passed on to the second generation. But we do not yet know which changes these are and how far down the line these epigenetic changes can be transmitted.
That means that the grandchildren of trauma victims can also have psychiatric problems based on experiences suffered by their grandparents?
Mansuy: Yes, descendants can also have symptoms. The nature of the symptoms depends on the trauma. In cases of childhood abuse, this could be depression, risk-driven and/or antisocial behavior, memory problems and even physical dysfunctions such as glucose/insulin or lipid metabolism disorders. However, research into heredity in humans is more complex than in mice, where they all have the same genome and are kept under the same conditions. In humans, external influences are much more diverse and therefore more difficult to attribute.
You postulate that we can optimize our epigenome. How can we do this?
Mansuy: First I’d like to make clear that there are limits to the scope of our influence. If you suffer from depression due to a traumatic childhood experience, for example, I’m not claiming that you can repair your badly damaged epigenome just by eating well or doing more sport. We can’t eradicate this negative experience; but we do know that psychotherapy can alter the epigenome, as can good nutrition or exercise. This can help people process their traumatic experiences.
If I said I’d like to be happier and healthier, what would you advise me?
Mansuy: To do all the things we know already: take good care of yourself, eat well, i.e. fruits and vegetables, and a balanced and varied diet. The epigenome needs vitamins.
Your book contains whole tables of healthy foods – with liver also featuring prominently. This implies that it takes more than eating a pure vegetarian diet to develop a good epigenome.
Mansuy: These are just tips. It doesn’t make sense for me to issue strict instructions. If someone wants to eat meat, that’s their choice. If they can compensate for meat with vegetarian foods, all the better. My message is that eating a balanced and varied diet is best. We need a bit of everything.
What do you do for your epigenome?
Mansuy: I eat healthily and a bit of everything. I try to eat lots of raw foods and I avoid processed products. I also do a lot of sport. I go jogging, and I work while training on my cross trainer – to save time.
You’ve written a popular book on a complex subject. What are you hoping to achieve with it?
Mansuy: I’d like people to learn more about the epigenome and to understand that this genetic information is hereditary. In other words, our lifestyle can have an impact on our children and grandchildren. It may be difficult to accept, but we should be aware of it.
The professor of neuroepigenetics at the Medical Faculty of the University of Zurich and at ETH Zurich is engaged in research on the epigenetic basis of complex brain functions and the mechanisms of how acquired characteristics are passed down through the generations. Based on experiments with animals as model organisms, her research studies the molecular effects of life experiences, such as traumatic events in childhood, on the physical and mental health of those directly affected and their descendants. Isabelle Mansuy is playing a pioneering role in the new research field of epigenetics.
Isabelle M. Mansuy, Jean-Michel Gurret, Alix Lefief-Delcourt:
Wir können unsere Genes steuern! Die Chancen der Epigenestik für ein gesundes und glückliches Leben; Piper, 2020.
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