The effects of starvation can be passed down for as many as three generations, at least in worms, and result in the great-grandchildren living 1.5 times as long as the oldest generation, a new study by Israeli and American researchers has found.
“Hunger affects genes connected to nutrition, and their metabolism changes,” said Tel Aviv University neurobiologist Oded Rechavi, the lead author of the study.
“The issue of life extension is still rather mysterious, but one thing we do know is that when you eat less and are in a state of moderate hunger, you live longer," he said. "We managed to extend these worms’ lives significantly, but we haven’t proven this directly, so more research will be needed to decode the mechanism.”
The study, which was published this month in the scientific journal Cell, is the first to show that altered environmental conditions are sufficient to cause hereditary changes in worms, said Rechavi.
“Previously, nobody had yet shown that it’s enough to change the worms’ environmental conditions to cause heredity that isn’t dependent on DNA,” he said. “Because restricting calorie intake apparently extends life, the great-grandchildren of our famished worms lived 1.5 times longer than ordinary worms — despite the fact that they ate no less than any other worm.”
The hunger study delves into the field of epigenetics, or genetic changes caused by the environment. These environmental changes don’t actually alter an organism’s DNA, but do affect the way certain genes express themselves.
On the same day that Cell published the hunger study, the journal Science published a study by another group of researchers that found a similar response in mice. But deciphering the mechanism in worms and mice is just the beginning, said Rechavi.
“Epigenetic inheritance also exists in human beings, but time will tell whether the same mechanisms are at work in them,” he said. “If so, this could mean reassessing the entire concept of heredity. For instance, it could be that genetic testing of groups at risk of different diseases should include genes other than those transmitted through heredity. If so, that would be good news, because this is a process in which, at least in theory, we could intervene early to prevent pathology.”
The best-known example of epigenetic inheritance among people took place at the end of World War II, said Rechavi.
“For many years, it’s been very hard to explain the inheritance of many characteristics on the basis of genetics alone,” the scientist said.
“The most famous example of epigenetic inheritance in humans is the famine in Holland at the end of World War II. Contrary to what classic Darwinism would have predicted, the children of Dutch famine victims showed various effects of their heredity that appeared to be a kind of compensation for their parents’ starvation. For instance, they had a higher tendency toward diabetes, even though their DNA could not have been influenced by their parents’ hunger.”
The Netherlands is not the only country where human heredity appears to have been affected by the environment, he said.
“Proof of this has also been found in other places, like China, Russia and Sweden,” said Rechavi. “Nevertheless, it still wasn’t clear whether what was happening was an environmental influence on sex cells, a psychological or cultural influence by the parents, or a true epigenetic effect.”
In the hunger study, Rechavi and his team starved microscopic worms and managed to detect two genes responsible for epigenetic transmission to future generations, one called RDE-4 and one called HRDE-1. These genes produce tiny molecules whose function is to transmit the physiological expression of genes from generation to generation.
The other researchers included Leah Houri-Ze’evi and Sarit Anava of Tel Aviv University, Wee Siong Sho Goh and Gregory J. Hannon from the Cold Spring Harbor Laboratory in New York, and Sze Yen Kerk and Oliver Hobert from Columbia University Medical Center.