Epigenetics – Where Heredity and Environment Meet


Can grandparents’ behavior in childhood affect the health of children and grandchildren? In this article, we will look at a new and exciting field of research, where researchers attempt to find answers to whether the effects of the environment and lifestyle can be transferred to our descendants

There is an increasing focus on what promotes and what damages our health. From magazines, newspaper covers, advertisements and TV programs to health magazines and other professional health actors, efforts are being made to inform us about the path to optimal health. The newspapers, and especially the front pages, overflow with well intentioned health advice. Here you can learn to eat as heart-friendly as Bill Clinton, remove extra kilos and attain perfect digestion, as long as you remember buy the newspaper.

If you haven’t jumped on the merry-go-round yet, the health circus probably has a newspaper cover tailored to your needs the next time you check out at the supermarket, in the middle of chocolate bars, tobacco and other temptations. The main character in the menagerie mostly seems to be me, the consumer, who with a hectic lifestyle is expected to over perform in all arenas of life. For this you need good health. Health sells, and good health gives status. The authority of additional pounds is out, a fit body is in.

Public health has improved considerably in many areas over the last few generations thanks to, among other things, health information. Through years of solid research, we know that our lifestyle affects our physical and mental health. However, do my habits only have an effect on myself, and am I living healthy solely for my own sake? On the basis of a number of observations, experiments and larger studies in recent years, people have seriously

begun to ask questions about whether our habits also affect our own genetic material and thus potentially our descendants.

Into the woods

One of the first sprouts of understanding that we live less for ourselves than what has hitherto been assumed to be genetically acceptable, one had, of all place, to go into the Norwegian spruce forest to find. Perhaps a favorable starting point for reassessing who we are and what we live for.

In the 1970s, Norwegian forest researchers, including the head of the Department of Plant and Environmental Science at Ås, Øystein Johnsen, discovered that the trusty Norwegian spruce did not always behave as expected. As is known, the spruce tree cannot run away from external adverse influences, but has a good ability to adapt to the environment it grows in. It is observed that genetically identical spruce seeds, which had the same “parents”, produced trees with different growth rhythms depending on whether the origin produced the seeds in warm or cold years. The effect on the growth rhythm proved to last a lifetime. Seeds formed under higher temperatures produce trees that shoot buds earlier in the spring and set buds later in the autumn than trees originating from seeds formed in colder years.

This could not be explained on the basis of classical genetic understanding. It has gradually come to the understanding that external influences can affect the seed to a certain extent during a sensitive period during seed formation. We thus see that external factors to which the “parents” were exposed left their mark on the next generation of fir trees. This is explained on the basis of so-called epigenetic mechanisms.

Transgenerational effects of lifestyle

Have you considered that even though all our cells have identical DNA or genetic material, they are nevertheless very different in structure and function. An important reason for this is that there are mechanisms closely linked to the DNA molecule that control the activity of the genes.

Epigenetic markers (eg for DNA methylation, histone modification) along the DNA molecule can tell genes to turn off or on, or to keep a low profile, for example. When a cell divides, the same gene expression is retained so that, for example, liver cells continue to produce liver cells and not nerve cells or skin cells. This type of “memory” or epigenetic inheritance that is transferred from cell to cell has been known for a long time. It is also known that external factors can affect the epigenetic mechanisms and thus also our genes.

In this way, epigenetics becomes a meeting place between heredity and environment. In connection with the formation of germ cells and during fertilization, the epigenetic markers in the germ cells are erased so that the fetus starts its development with a “blank sheet of paper”, so to speak. However, it appears that some epigenetic markers escape this erasure. In this way, it is possible that the effects of environmental influences that the parents have been exposed to can be transferred to the next generation.

Animal studies

Researching transgenerational effects in humans has its natural challenges, as such studies will take a long time to complete because many years pass between each new generation. Mice and rats have shorter lifespans and the opportunity to observe several generations within a relatively short time is therefore present. There are also ethical dilemmas linked to research on humans in this area.

In an animal experiment, 15-day-old mice were exposed to an enriched environment that included “toys”, increased social stimulation and voluntary physical activity. The control group did not have access to such “luxury”. It was observed after a period that the mice that lived in an enriched environment, among other things, had better memory than the mice in the control group. Furthermore, it was seen that their offspring also had better memory, of course only in the first part of their lives. This may indicate that their good lifestyle had a positive effect not only on themselves, but on their own offspring.

Professor Skinner at Washington State University did an experiment with pregnant rats. He exposed them to two types of sprays (a pesticide and a fungicide) that are used in connection with grape production on the west coast of America. He observed that the pregnant rats had offspring with reduced sperm production and increased infertility. This effect persisted in 90 percent of the male rats in all four subsequent generations examined. Upon closer examination of the rats, findings were made which indicated that the pesticides had reduced gene expression in the sperm via epigenetic mechanisms and thus led to increased infertility. Again, we see how an external influence can have unfortunate consequences in several subsequent generations. This type of inheritance is not due to changes in the DNA sequence or the genes themselves, but in the epigenetic control mechanisms that regulate the activity of the genes.

At the University of Edinburgh, experiments have also been carried out with pregnant rats. They were exposed to stress hormones during pregnancy and it was observed that the young had a changed stress response throughout their lifetime. Not only that, the offspring got even offspring with altered stress response. It was thus observed that an environmental factor (stress hormones) to which pregnant rats were exposed had an effect on both “children” and “grandchildren”. Such observations help support the understanding of transgenerational epigenetic inheritance.

Tansgenerationial effects in humans

In the same way that altered stress responses have been observed in the offspring of pregnant rats that were exposed to stress hormones, similar effects have also been seen in humans.

Among other things, altered stress responses have been observed both in children who were born to survivors of the Holocaust, and also in small children (one year old) who were born to pregnant mothers who were exposed to great stress during the terrorist attacks in New York in 2001.

In the far north of Sweden, in the municipality of Överkalix in Nordbotten County, a few years ago a startling discovery was made by Professor Lars Olaf Bygren, who is affiliated with the institute for preventive nutrition at the Karolinska Institutet. In the 19th century and the beginning of the 20th century, Överkalix was still a fairly isolated area and poor harvests often led to famine.

The crops varied from year to year and there is good historical data on both crops, food prices and causes of death in the municipality. Professor Bygren was interested in whether there was a connection between access to food for people born at that time and measurable health effects on children and grandchildren.

Bygren’s findings were highly interesting. He observed that access to food, especially before puberty (8-12), produced significant health effects in children and grandchildren. Boys who had great access to food at this age had sons and grandsons who lived significantly shorter (6 years) compared to descendants of boys with reduced access to food aged 8-12. Only one year with a large supply of food during this age period was sufficient to reduce the life expectancy of the son and grandson. Later analyzes have found the same effect in girls. However, this transgenerational effect appears to be genderspecific, that is, boys influenced their sons and grandsons, while girls influenced their daughters and granddaughters. When it came to heart disease, he found a clear connection between reduced food access in fathers (aged 8-12 years) and a reduced risk of death from heart disease in his sons. If the mother had high food access during this period, it led to areduced risk that her children would die of heart disease.

Transgenerational risk of diabetes

When it came to diabetes, it was seen that high access to food by fathers (in the period 8-12 years) led to sons and grandsons having a fourfold increased risk of dying from diabetes. If the father, on the other hand, had reduced access to food, the children and grandchildren had a reduced risk of dying from diabetes. In a long-term study ongoing at the University of Bristol, it has been seen that boys who started smoking before the age of 11 had sons who had a higher BMI (body mass index) at age 9.

You are what your parents and grandparents ate

In general, few studies of this type have been carried out, and more studies are needed to determine how and to what extent our own behavior affects our descendants. We have often heard that “you are what you eat”. Based on what is known today about transgenerational epigenetic inheritance, we may also have to include that “you are what your parents and grandparents ate”. It is a new thought for many people. Transgenerational effects have so far been observed on several organ systems, and the most important environmental factors that can lead to lasting epigenetic changes appear to be diet, stress, nutrition in fetal life, and toxins.

Although there are currently not many answers, it is becoming clear to us that what we are exposed to throughout life, what choices we make and habits we adopt, not only affect us, but can also affect the lives of our children , grandchildren and possibly even more relatives. Our genes are not locked away in our cells, unaffected by how we live. We have the genes, which we received from our parents, “on loan” and we want to pass them on to our descendants in the best possible condition. With such an attitude, the focus on living healthy is put into a greater perspective. From being solely about my own health, health becomes something that also concerns my descendants. Maybe it’s healthy too?

Have you already passed on the genes to the next generation? Do not despair. You may still be able to give future generations a better starting point by encouraging your own children and grandchildren to appreciate a healthy lifestyle.

Reference

  • Junko A. Arai, Transgenerational Rescue of a Genetic Defect in Long-Term Potentiation
  • and Memory Formation by Juvenile Enrichment, The Journal of Neuroscience, 4 February 2009,29(5): 1496-1502
  • Michael Skinner et al, Epigenetic Transgenerational Actions of Endocrine Disruptors and Male Fertility, Science 3 June 2005: Vol. 308 no. 5727 pp. 1466-1469
  • Rachel Yehuda et al, Transgenerational Effects of Posttraumatic Stress Disorder in Babies of Mothers Exposed to the World Trade Center Attacks during Pregnancy, The Journal of Clinical Endocrinology & Metabolism July 1, 2005 vol. 90 no. 7 4115-4118
  • G Kaati, LO Bygren and S Edvinsson, Cardiovascular and diabetes mortality determined
  • by nutrition during parents’ and grandparents’ slow growth period, European Journal of Human Genetics (2002) 10, 682-688
  • Marcus E Pembrey et al, Sex-specific, male-line transgenerational responses in humans,
  • European Journal of Human Genetics (2006) 2, 159-166

Allan Fjelmberg, MD, MPH, DipIBLM

As a Norwegian based medical doctor certified in Lifestyle Medicine he currently serves as the medical director of Skogli Health and Rehabilitation Center, Lillehammer. Through consultations, presentations, articles and other public health-related activities, he motivates people to utilize the potential that a healthy lifestyle has both in prevention and treatment of disease.

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