In the winter of 1944, the Nazis blocked food supplies to the western part of Holland, creating a period of rampant famine and devastation.
The impact of starvation on expectant mothers produced one of the first known epigenetic “experiments” – changes resulting from external rather than genetic influences – which suggested that the body’s physiological responses to hardship could be inherited. How this actually worked remained a mystery.
In a paper published recently in the journal Cell, Tel Aviv University and American scientists investigated a genetic mechanism that passes on the response to starvation of C. elegans nematodes worms to subsequent generations of the invertebrates, with potential implications for humans also exposed to starvation and other physiological challenges, such as anorexia nervosa.
Dr. Oded Rechavi, Dr. Leah Houri-Ze’ev and Dr. Sarit Anava of TAU’s faculty of life sciences and the Sagol School of Neuroscience, Prof. Oliver Hobert and Dr. Sze Yen Kerk of Columbia University Medical Center and the Howard Hughes Medical Institute and Dr. Wee Siong Sho Goh and Dr. Gregory Hannon of the Cold Spring Harbor Laboratory and the Hughes Institute published their research in the journal, Cell.
“There are possibly several different genetic mechanisms that enable inheritance of traits in response to changes in the environment. This is a new field, so these mechanisms are only now being discovered,” said Rechavi. “We identified a mechanism called ‘small RNA inheritance’ that enables worms to pass on the memory of starvation to multiple generations.”
RNA molecules are produced from DNA templates in response to the needs of specific cells. “Messenger” RNA molecules (mRNAs) contain instructions for the production of proteins, which service cells and allow them to function.
But other RNA molecules have different regulatory functions.
Small RNAs are one species of these regulatory RNAs – short molecules that regulate gene expression, mostly by shutting genes off, but sometimes by turning them on.
Rechavi first became interested in studying starvation-induced epigenetic responses following a discovery he made as a post-doctoral student in Hobert’s lab.
“Back then, we found that small RNAs were inherited and that this affected antiviral immunity in worms. It was obvious that this was only the tip of the iceberg,” he said.
In the course of the new study, worms were starved at a young age and reacted by producing small RNAs, which function by regulating genes through a process that is known as RNA interference. The researchers discovered that the starvation-responsive small RNAs target genes that are involved in nutrition. More important, the starvation-induced small RNAs were inherited by at least three subsequent generations of worm specimens.
“We were also surprised to find that the great-grandchildren of the starved worms had an extended life span,” said Rechavi. “To the best of our knowledge, our paper provides the first concrete evidence that it’s enough to simply experience a particular environment, such as one without food – for small RNA inheritance and RNA interference to ensue. In this case, the environmental challenge is starvation, a very physiologically relevant challenge.”
RNA inheritance could prove to be an important genetic mechanism in other organisms, including humans, acting parallel to DNA.
“This could possibly allow parents to prepare their progeny for hardships similar to the ones that they experience,” Rechavi said.
The researchers are now studying a wide variety of traits affected by inherited small RNAs.
SHOULD INFANTS NOT GO ON AIRLINE FLIGHTS? Infants are not given a seat in a commercial airline fight, but are held in their parents’ arms or laps. But even though it is standard practice, it could be very unsafe – and not only regarding safety in the event of a crash. In a first-of-its- kind study, researchers at University Hospitals Rainbow Babies & Children’s Hospital in Cleveland analyzed pediatric medical emergencies involving 7,000 medical emergencies involving children on flights worldwide between 2010 and 2013. They found 90 percent of deaths occurred in children under the age of two, suggesting that it might be wise not to take them on planes at such a young age. Death most commonly occurred in previously healthy children under the age of 24 months and in children with a preexisting medical condition.
Pediatrics Prof. Alexandre Rotta, the study’s principal investigator, said that of the 7,573 reported emergencies, 10 resulted in death, and six had no previous medical history.
Four passengers had preflight medical conditions, including two children traveling to access advanced medical care. Dr.
Rotta speculates these infants were at increased risk from exposure to a hypoxic cabin environment or by sharing a seat with an adult and co-sleeping during a long flight, but there could also be another as-yet unknown factor.
“I hope our findings lead to further research on this important subject,” said Rotta. “It is my belief the pattern we discovered should promote the development of preventative strategies and travel policies to protect the health of all pediatric airplane passengers, especially infants.”
RESUSCITATING WOMEN GIVING BIRTH Electrical failure of the heart during delivery is uncommon, affecting one in 12,000 women, but resuscitating them requires special techniques. The statistics have not changed in the past decade, despite the rising childbearing age, said Dr. Sharon Anav, an anesthesiologist and intensive care specialist at Jerusalem’s Shaare Zedek Medical Center.
Anav was a member of a team that recently studied the issue, including hospital preparedness for such events. The team published an article with its findings and recommendations on how to get organized and what physical signs should arouse suspicion that such an event may occur.
Anav said they she received a query even from the American Heart Association, which invited her to help prepare an addition memorandum of understanding on resuscitating such women. Anav was recently named chairman of the Israel Resuscitation Society.