A new Swedish study shows that what grandfather ate in his youth impacts mortality two generations later. If grandpa had access to an abundance of food in the years immediately before puberty, his grandsons were found to have an increased risk of cancer. This connection existed only along the male lineage.
The researchers' results are similar to the previous, smaller Överkalix study, which attracted attention when it was published in 2002.
In the Överkalix study, Lars Olov Bygren and his colleagues wanted to investigate how hunger and malnutrition in the 19th century had affected the subsequent three generations in a small Swedish community. Bad and good crop harvest years resulted in big differences in access to food in the 1800s.
The study results were surprising. It turned out that overeating in the good years, and not hunger, seemed to affect the health of later generations. When paternal grandpa ate a lot in his pre-pubertal years, this shortened the life of his grandsons by six years.
There isn't an obvious explanation for this, but researchers believe it has to do with how genes are affected by environmental factors, called epigenetics.
9000 grandparents
The researchers from Stockholm University have tested whether the connection found in the Överkalix study would yield similar results in their new study. In the new study, they examined 9000 grandfathers, their children and 11 000 grandchildren, making the sample 40 times larger than the earlier study.
The researchers used crop harvest statistics from 1874 to 1910 to assess the grandparents' access to food during pre-puberty, defined as ages 9 to12 for boys and 8 to10 for girls. This is a slow growth period, where the gametes, or reproductive cells, are particularly vulnerable to changes, according to the researchers.
The crop yields could be very different from year to year. Researchers presumed that children ate more than usual in the years and places where food had been plentiful.
The researchers also looked at the grandchildren's mortality data from 1961 to 2015.
Grandsons more often died of cancer
It turned out that the grandsons of well-fed paternal grandfathers more often died of cancer. The researchers found no such relationship among the parent generation or in the granddaughters. No difference in grandsons' mortality risk was apparent when the paternal grandfather had low or moderate access to food.
Controlling for other factors, such as the use of pesticides and smoking, yielded the same results.
"The relationship between good food availability and increased mortality was strengthened after looking at other factors, including social conditions in families like education, family size and income. Introduction of chemical pesticides was limited in the end of the 1800s and it's not likely that it would have led to new, large-scale mutations," Denny Vågerö stated in a press release from Stockholm University.
He is a professor in the Department of Public Health Sciences and one of the authors of the study.
The Överkalix study found a higher incidence of cardiovascular disease and diabetes. These connections were weak in the new study, which showed cancer to be the main cause of numerous deaths among grandsons.
"The most reasonable explanation would be that boys,' but not girls,' germline cells are vulnerable to epigenetic change like nutritional effects during pre-puberty. If that is the case, these changes might be passed on to following generations, something that has also been shown in animal experiments," says Vågerö.
Just why more food in the years before puberty seems to affect grandsons' mortality is something that needs to be investigated more closely.
How we live affects gene expression
The plentiful food connection can't be explained by inheritance alone, which leads the researchers to believe that the result has to do with epigenetics. The word itself means "outside of genetics," and epigenetics thus links inheritance and the environment.
By way of example, if no one in your family has any particular musical ability, but you work and get good at it, it doesn't mean that your children will be born with genes for musicality. But environmental factors can in other instances leave traces in our genes. Identical twins can grow up to be quite different.
How we live, what we eat and what we experience can affect which genes are expressed in our cells, for example making us more or less vulnerable to diseases. The DNA itself does not change, but some genes may become active or inactive due to environmental impacts.
Research suggests that these changes can also be inherited, not just between parents and children but also over several generations.
Both physiological and psychological factors
Recent research has revealed how epigenetic changes appear to affect both the descendants' physiological and psychological health. One such heritable factor is damage from environmental pollutants.
A 2016 experiment showed that obese male mice could transmit health problems to their first and second-generation male offspring.
In another experiment from 2013, researchers exposed a group of mice to the scent of the organic compound acetophenone, which has a bit of an almond smell. At the same time, the mice received a mild electric shock on the soles of their feet, which startled them.
Surprisingly, it turned out that the offspring of these mice also flinched at the almond scent. They had inherited the fear, as did the second-generation offspring, even though they had never been shocked or seen their parents shocked.
Some research also indicates that trauma in humans can be passed on for up to several generations.
