Sarah was 90 years old and Abraham 100 when their son Isaac was miraculously conceived and born. Today, young women often delay childbirth, feeling they want to focus on studies or a career or not finding a suitable partner. Throughout much of the world, increasing numbers of women are delaying having their first child until they are in their late 30s and even into their 40s, thinking they still have time to get pregnant with a healthy fetus.
However, their eggs rapidly deteriorate at this age, and even with in-vitro fertilization, their prospects of conception are far from guaranteed.
Reversing that deterioration is the ultimate goal of molecular biologist Dr. Michael Klutstein, head of the chromatin and aging research lab in the Faculty of Dental Medicine at the Hebrew University of Jerusalem (HUJ). This possibility has now come one step closer with recent research from his lab, carried out by doctoral student Peera Wasserzug-Pash. in collaboration with clinicians from the Hadassah University Medical Center and Shaare Zedek Medical Center in Jerusalem.
Their findings have just been published in the journal Aging Cell under the title “Loss of heterochromatin and retrotransposon silencing as determinants in oocyte aging.”
In humans, egg cells begin to accumulate damage to their genetic material when a woman is relatively young. Often, by the time she is in her late-30s, her eggs have got so much damage to the DNA that they cannot mature and be fertilized. Klutstein’s team successfully identified one of the aging processes that prevent the successful maturation of an egg cell. Most importantly, the loss of the regulatory processes generally stops the damaging parts of DNA from becoming active.
It is, in many ways, a strange idea to think that parts of our DNA contain sections of genetic material that can be damaging. About half of our genome is made of virus-like sequences or fragments of viruses that can cause considerable damage to the DNA if allowed to be activated through expression.
This idea has been studied extensively and was discovered by American cytogeneticists. Dr. Barbara McClintock received the 1983 Nobel Prize in Physiology or Medicine for her work on this topic. She received the prize for her discovery of genetic transposition. She died in 1992 at the ripe old age of 90, and, as of 2022, she remains the only woman who has received an unshared Nobel Prize in that category.
The aging process causes the system’s failure to keep these damaging elements repressed and inactive. Using mouse and human egg cells, Klutstein and his team identified the details of these processes and showed how they are interrelated and ultimately prevent an egg cell from maturing.
To confirm their findings, the team then used chemicals that mimic the actual processes to stop the repression of sections of the egg cell’s DNA and free the DNA-damaging viruses. Reproducing the aging processes artificially enabled the team to link the loss of genomic regulation processes and the expression of damaging elements in aging egg cells.
The final stage of their research-tested ways to reverse the destructive aging processes at work in an egg cell. If viruses or parts were released and activated in aging eggs, they thought that perhaps, anti-viral drugs could prevent this process and the resulting damage.
In their paper, the researchers showed that anti-viral drugs reversed the process in mouse egg cells and returned to their former youthful selves. There has also been similar success using genetic manipulation to insert two genes into the mouse egg cell DNA; the implanted genes produce enzymes that prevent the chain of events that leads to the activation of the damaging parts of the DNA. “Within a decade,” concluded Klutstein, “I hope we will be able to increase fertility among older women using anti-viral drugs.”