18,000 people died of starvation during the Dutch Hunger Winter in 1944–45. But traces of the famine persisted much longer than that. Children born during the period when their parents were starving have been shown to be at greater risk of developing type 2 diabetes and cardiovascular disease as adults. How can that be?
The explanation seems to lie in what is called epigenetics. This can be described as a kind of biological memory, which can change how the body reacts to things like starvation, infections or smoking – a memory that can sometimes be passed on to the individual’s children and even grandchildren. In this way, different genes can become more or less active, without changing the DNA itself. Some changes remain for a very long time, while others are removed after a short period.
Not just negative effects
Anita Öst and Maria Lerm have both been interested in epigenetics in their research, but from different aspects. Anita Öst researches how parents’ lifestyles affect the metabolism of the next generation. She has for example studied fruit flies and shown that the risk of obesity in future generations is affected by whether the father is starving overfed.
Epigenetics is programmed for survival during starvation, but it has negative consequences for the metabolism of future generations, especially if they grow up having food in abundance.
“In my field, when it comes to metabolism, the epigenetic effects of starvation or overfeeding are often negative. So I found it interesting when Maria started talking about how some epigenetic changes that affect the immune system can be positive,” says Anita Öst.
As an example, a study by researchers at Bonn University a couple of years ago pointed out that male mice having had a candida fungal infection had sons who were at lower risk of dying from such an infection. The protective effect applied also to the next generation, the male’s grandchildren.
Maria Lerm and Anita Öst combined their expertise on infections and how different types of environmental factors have epigenetic impact over several generations. Together with their colleagues Shamila Alipoor and Parisa Norouzitallab, they have gone through the scientific literature and written a perspective article on the current situation in the research field.
They suggest that the father’s exposure to diet, stress, harmful substances and infections can affect his child’s and grandchild’s immune system through epigenetic mechanisms. Where this results in enhanced protection against disease, it could give his descendants an evolutionary advantage. The hypothesis now presented by the researchers has to be tested through research to hold true.
Why focus on the father?
Their focus on the father’s influence on his future children may seem unexpected, but there is an explanation.
“We don’t think that the father’s role is more important, rather the opposite. The mother’s epigenetic influence on the baby is probably greater. However, since the mother has an influence on the embryo and foetus for a very long time, it’s more difficult to discern the effects of different exposures. It’s easier to follow epigenetic effects on the male side, because the time frame is so short; the sperm delivers the genetic material to the egg and that’s it. It’s only at that very moment that biological information can be transferred from the father. This makes it easier to figure out how it works,” says Anita Öst.
It is still unclear exactly how the transfer of biological information about an infection or similar that the father experienced many years earlier is transferred to the child. The epigenetic code consists of chemical modifications, such as DNA methylation, and it has been well established that large parts of this code are erased in the embryo.
Nevertheless, it seems that the biological information is somehow preserved until the foetus has been established, and then reintroduced into its DNA. Scientists are now looking for mechanisms for this.
Long-term effects of teenage lifestyle
If our lifestyle and diseases can affect future children, how far back in time could it go? Some studies suggest decades.
“It may be important to be aware that for boys, puberty and the time before appears to be a sensitive period when it comes to smoking, for example. According to a Norwegian study, the risk of children developing asthma increases if fathers smoked when they were younger than 15. So these are long-term effects that can have consequences far beyond the individual’s health,” says Anita Öst.
When it comes to smoking, the scientific community has long studied what happens in the body when it is exposed to smoke, which contains toxic hydrocarbons.
“There’s an epigenetic signature that has been very well studied and has been found in a large number of organisms. It’s an evolutionarily preserved defence system that helps the body protect itself from toxic hydrocarbons. We’re not the first organisms in the history of the Earth to be exposed to harmful hydrocarbons,” says Maria Lerm.
Epigenetic regulation of this defence system against toxic hydrocarbons has been linked to respiratory hypersensitivity and developing asthma. It is an example of the fact that biological memory sometimes has positive and sometimes negative effects.
Biological memory can be rewritten
Unlike the genes we are born with, which we cannot do anything about, the biological memory – the epigenome – is not set in stone, according to Maria Lerm:
“Many studies show that these are dynamic processes. The scale ranges from changes that are very stable to those that are very, very dynamic. That's the beauty of epigenetics.”
Article: , Shamila Alipoor, Parisa Norouzitallab, Anita Öst and Maria Lerm, (2025), Journal of Internal Medicine, published online 29 May 2025, doi: https://doi.org/10.1111/joim.20094
