Princeton molecular biology professor Coleen Murphy and Shijing Luo may have found a way to slow down the ticking of a woman’s biological clock: worms.
Murphy, Luo and other members of a research team found that as worms age they produce eggs that degrade more quickly. Just as in humans, the quality, not the quantity, of the eggs is the limiting factor in determining fertility. An increase in the production of proteins called transforming growth factor beta is directly linked to the lower quality of the unfertilized eggs. TGF-beta proteins are found in most mammals, including humans. These findings may present a way to increase fertility in humans.
“It feels good to know that what you are working on is likely to be beneficial for a lot of people and families in the future,” Luo said in an e-mail. “Even when there are obstacles in experiments, knowing this gives me the power to move on.”
Murphy and the research team modeled issues of aging and longevity using C. elegans worms. Worms make a good research target for fertility studies because their short lifespan allows researchers to study fertility in an easily observable span, Murphy said in an e-mail.
“Worms are a great system because they ‘live fast’ and because they share many genes with humans,” she added. She said that many processes that affect the longevity of worms have also been found to be important in higher organisms.
Among these shared genes are the TGF-beta proteins. These proteins damage egg cells as the worms exit their reproductive stage and play a role in determining cell specialization.
As the basis for her doctoral work, Luo created mutated worms that had lower TGF-beta activity. She then isolated unfertilized egg cells, called oocytes, both from these worms and from normal ones and compared the quality of the eggs.
The mutated worms produced more healthy eggs even as they aged and had an increased reproductive span as a result, she found.
Murphy said that because of the similarity in genes between worms and humans a similar result might be found in humans.
“It seems pretty clear that worm and human oocytes age in similar ways,” she said. “Given this finding, I think that someday we could use this information to improve oocyte longevity.”
Both Murphy and Luo have had a sustained interest in the field of aging. Murphy said she believes that there are large biological and philosophical questions in the areas of aging and fertility, but the biological ones can be answered through creatures as different from humans as worms.
But it could take a long time for Luo’s research to have an impact on human reproduction.
“Basic research usually serves as the foundation for translational research and practical/clinical studies, and can take a long time to become applied, and this is influenced by many factors,” Luo said.
Even if the quality of eggs does not deteriorate, many other factors could make it difficult for women to reproduce later in life. The researchers found that even though the mutant worms had a longer reproductive period, worms which attempted to reproduce in the last third of their lives found the process life-threatening.
Luo published a paper in Cell, a biology journal, documenting the team’s research with Murphy and its implications. She said that she is interested in the fields of fertility and aging in part because of her background as a woman in higher education. This research becomes more relevant “as more and more women (especially professionals) have children later in life,” she said.