Malnourishment in the womb causes genetic changes that can still be seen when people reach middle and old age, according to new research that shows how strongly environmental influences can interact with the human genome to shape health.

A study of children born during the Dutch “Hunger Winter”, a famine that struck at the end of the Second World War, has found that some still bear its lasting genetic legacy more than six decades on.

The results offer some of the best evidence yet for the importance of epigenetics, a process by which environmental factors can change the way genes are switched on and off in the body.

Epigenetics suggests that the genome can “remember” certain influences to which it is exposed, particularly early in life, which cause modifications to DNA that in turn alter the way it operates. On occasion, these changes may even be passed on from one generation to the next.

Such epigenetic effects are increasingly thought to play an important part in the influence of DNA over health, allowing nurture to combine with nature to affect growth, development, metabolism and susceptibility to disease.

The Hunger Winter of 1944 to 1945, when parts of the Netherlands experienced a severe famine because of a German food blockade, has long intrigued researchers in epigenetics, because it provided a natural experiment for studying how difficult environmental conditions might affect children.

Previous research has found that children whose mothers became pregnant during the famine were at high risk of a wide variety of health problems, including diabetes, obesity and cardiovascular disease. They also went on to have children who were more likely than usual to be born underweight.

This observation has led many scientists to propose that epigenetic effects might be responsible. The hypothesis was that the experience of growing in a womb short of nutrients might have caused genes to be altered to support a thrifty metabolism.

Such a mechanism could have evolved because the uterine environment was usually a good guide to the conditions that would prevail once a child was born, so encouraging it to store energy and use it sparingly would have had survival advantages.

This has now found support from the new study, led by Bastiaan Heijmans, of Leiden University in the Netherlands. Details are published in the journal Proceedings of the National Academy of Sciences.

One of the main mechanisms of epigenetics is a process called methylation, by which chemical groups are added to DNA to alter its function. Dr Heijmans’s team examined this in people born during the Hunger Winter, and their siblings born when there was no famine.

Even though these people are now in their sixties, the imprint of the famine can still be seen in their genomes, in the shape of methylation patterns on a gene called insulin-like growth factor 2 or IGF2.

People who were exposed to famine during the first 10 weeks after their conception had much less methylation of the IGF2 gene than did their siblings of the same sex. No effect was seen, however, among those who were 10 weeks away from birth when the famine began.

The results seem to indicate that early prenatal development has a strong effect on epigenetics, and can reprogramme the genome in ways that last throughout life. The scientists are now seeking to investigate whether this correlates with health effects.

Dr Heijmans said: “Our study provides the first evidence that transient environmental conditions early in human gestation can be recorded as persistent changes in epigenetic information.

“Understanding how epigenetic control depends on early exposure may shed light on the link between development and health over the lifespan and ultimately suggest new ways to prevent human disease.”

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