Epigenetics Research Could Help Unlock Secrets to Longer, Healthier Lives
04/01/2025
By Brooke Coupal
At first glimpse, C. elegans and people appear to have nothing in common.
The nematode worm, whose full scientific name is Caenorhabditis elegans, measures about one millimeter in length, approximately the size of a grain of sand. Its body is transparent and lacks most complex organs, including a heart and lungs. Its average lifespan is 20 days, during which time it produces about 300 offspring.
Despite the clear differences, these microscopic worms can provide valuable insights into how people can live longer and healthier lives.聽 鈥淎ll of life is connected to each other, so if we understand how something works in a worm, that means we understand more about how it might work in a human,鈥 says Teresa Lee, an assistant professor in the Department of Biological Sciences.
Lee has become well-acquainted with C. elegans over the past two decades, having studied millions of the worms. She brought her expertise to 51视频 in 2020 and created the Lee Lab, which researches C. elegans to better understand how the experiences of our ancestors impact our health and lifespan.
Lee鈥檚 research is contributing to the emerging field of epigenetics鈥攖he study of how our environment and behavior cause changes that affect the ways in which our genes function. Factors that can influence those changes include everything from trauma to healthy eating. A growing body of re - search points to the connection between epigenetics and diseases such as cancer, cardiovascular and autoimmune conditions.
Epigenetic changes can also impact longevity, with Dajani explaining that exposure to negative factors can accelerate a person鈥檚 aging clock, while positive factors can extend it.
鈥淲hat you eat, what you hear, who hugs you鈥 all play a role in how a person鈥檚 genes function, says Dajani, who added a disclaimer during the Dean鈥檚 Lecture Series talk: 鈥淓ven today in the lecture, I鈥檓 changing you.鈥
鈥淩esearch in epigenetics offers a powerful lens through which we can understand the complex relationship between genetic expression, disease and longevity,鈥 says Noureddine Melikechi, dean of the Kennedy College of Sciences. 鈥淏y exploring how epigenetics is passed down through generations, the work of Dr. Dajani and Dr. Lee sheds light on the way cultural, environmental and social influences shape an individual.鈥澛
Like a Box of Crayons
In 1998, C. elegans became the first animal to have its genome, or complete set of DNA, fully sequenced. The technologies and strategies developed from this discovery led the way for the Human Genome Project to be completed five years later. According to the National Human Genome Research Institute, the project 鈥済ave us the ability to read nature鈥檚 complete genetic blueprint for a human.鈥
Scientists had thought a person鈥檚 genetic blueprint would be much more complicated than that of a microscopic worm, but it turned out that both genomes consist of about 20,000 genes. The difference between C. elegans and humans is based, in part, on how those genes are packaged.
Lee says to think of it like a crayon box: Each animal is given its own box, representing the genome, and that box contains 20,000 different crayons, each representing a gene.
We are going to make very different pictures because we will choose to use different colors at different times in different places,鈥 she says. 鈥淭he beauty of biology is the genome knows which gene, or color, to use at which time, and part of that is based on how genomes are packaged.鈥
The entire genetic code of animals, from C. elegans to humans, is found in their DNA, which is packaged into chromatin鈥攁 mixture of DNA and proteins in a cell鈥檚 nucleus that helps keep DNA organized and compact. When chromatin is loosely packed, its DNA is more spread out, making it easier for the cell to access genetic information. This leads to gene expression, or the process by which the in - formation in a gene is used to determine how a cell functions and develops. In contrast, tightly packed chromatin prevents genes from activating because the DNA is more condensed, making it difficult for the cell to access that same genetic information.
鈥淭he DNA sequence is, for the most part, going to be the same in all your cells, but the packaging can be very different from cell to cell,鈥 Lee says. 鈥淎 skin cell will have the same sequence as a muscle cell, just with very different packaging.鈥
Longer Lifespan for Tiny Worms
Interested in what genetic information and packaging gets passed down from parent to child, Lee turned to C. elegans for answers.
Most C. elegans have male and female reproductive organs, meaning that one worm can make roughly 300 offspring on its own. As a result, their offspring are all genetically identical, because they inherit their genome from one parent. That parent, in turn, is also genetically identical to its parent, and that continues throughout the C. elegans鈥 lineage.
This differs from humans, who get half of their DNA from their father and half from their mother.
As a postdoctoral fellow at Emory University, Lee observed C. elegans in the same family gradually living 20% to 40% longer over many generations.
鈥淚n C. elegans, I can get 20 generations in a matter of months, which allowed me to see a gradual change in lifespan over time,鈥 Lee says. 鈥淭he worms鈥 fast generation time and high number of offspring allows us to do powerful genetic experiments.鈥
Lee could rule out changes in DNA sequence as a cause of the C. elegans鈥 longevity since the worms had the same genome as their ancestors. Instead, she discovered that the worms lived longer because they inherited high levels of condensed chromatin.
Environmental Factors at Play
When studying how chromatin is passed down between generations, Lee has focused on epigenetics, which is a major driver of chromatin packaging.
Epigenetics does not alter the sequence of DNA, but instead impacts gene expression by changing the compactness of chromatin. According to the U.S. Centers for Disease Control and Prevention, unlike genetic changes, epigenetic changes are reversible, which expands the possibilities for disease treatments.
Epigenetic changes generally reset in embryos to ensure that genes are expressed correctly during development, thus allowing different cell types, like muscle and skin, to develop appropriately. However, some epigenetic changes can be inherited by future generations, as seen in the C. elegans that lived longer. The compactness of the chromatin that the worms inherited can be attributed to epigenetic inheritance.
鈥淚n the long-lived C. elegans mutants that I studied, I showed that when you don鈥檛 erase epigenetic information correctly, you can change something as important as how long you live,鈥 she says. 鈥淭hat tells us that this resetting process between generations is really critical.鈥
In the Lee Lab at 51视频, Lee and her research team are further studying what epigenetic information gets inherited rather than reset. This will help develop a better understanding of the ways in which chromatin packaging shape gene expression and, ultimately, lifespan in C. elegans. The research is funded by a grant from the National Institute of General Medical Sciences worth more than $400,000.
Findings from the project could help shed light on the impact of epigenetic inheritance on humans, because gene expression in humans and C. elegans is similar.
鈥淏ecause I鈥檝e shown that C. elegans can pass down epigenetic changes through chromatin that impact lifespan, the question is, what about our own lived experience might also have the same effect?鈥 Lee asks. 鈥淭he packaging of genomes is so important to all life.鈥
Epigenetics and Disease
Scientists attribute the role that epigenetics plays in disease to the abnormal turning on or off of genes through the expansion or contraction of chromatin.
Studying the role of epigenetics in longevity can reveal mechanisms that slow or accelerate aging and age-related diseases. -Frédéric Chain鈥淭he question is, can chromatin information passed from parent to child affect the child鈥檚 disease status?鈥 Lee asks. 鈥淲e suspect it鈥檚 happening.鈥
Lee says the best evidence to support this hypothesis in humans came from studies on the Dutch Hunger Winter, a famine that occurred in the German-occupied Netherlands near the end of World War II. During that period, people had to live on rations, with some resorting to eating tulip bulbs and grass to survive. Thanks to well-kept health and lineage records, scientists found that the children and grandchildren of women exposed to the famine were more susceptible to obesity and diabetes, revealing a strong correlation between epigenetic changes and health outcomes across generations.
鈥淭hat鈥檚 one of the best datasets we have, but we still can鈥檛 be conclusive about those studies,鈥 says Lee, who adds that more research is needed to address uncertainties, such as whether the life experiences of the children and grandchildren contributed to their health outcomes.
One challenge for scientists studying the inheritance of epigenetics is the fact that humans live for decades (an average of 77.5 years in the U.S.) and lead complex lives.
鈥淭hat鈥檚 why doing this work with animal models, like C. elegans, is so important,鈥 Lee says. 鈥淚t builds our basis of understanding how epigenetics affects our biology and passes on through generations.鈥
While the Lee Lab looks at epigenetics鈥 role in the longevity of C. elegans, researchers there are also examining whether the worms are living a healthy life.
鈥淚f extended lifespan itself does not avail good health, what can we do to change that?鈥 questions Arthur Colunga, a senior biological sciences major who joined the Lee Lab as a first-year student.
Fr茅d茅ric Chain, an associate professor in the Department of Biological Sciences, studies the effects of epigenetics on evolutionary changes and is collaborating with the Lee Lab on its research.
鈥淪tudying the role of epigenetics in longevity can reveal mechanisms that slow or accelerate aging and age-related diseases,鈥 he says.
In a separate project funded by a $80,000 grant from the National Institute of Child Health and Human Development, Lee is investigating mutations in the protein CHD4 that, when influencedby epigenetics, may promote cancer in humans. The same protein in C. elegans is known as LET-418, and instead of causing cancer, a mutation in the protein decreases the worms鈥 fertility.
鈥淭he simplicity of C. elegans allows us to engineer the same human mutation into the worm version,鈥 Lee says. 鈥淔rom there, I can ask, 鈥業f I put this drug in the worm, does it improve their fertility?鈥 That will show me if I鈥檓 able to target the same mutation that may cause a very different disease in humans.鈥
Just as the sequencing of the C. elegans genome contributed to the success of the Human Genome Project, Lee鈥檚 research is laying the foundation for advancements that could one day improve health and the quality of life for generations.
鈥淚鈥檓 full of curiosity,鈥 Lee says. 鈥淯nderstanding the weird things that some organisms (like C. elegans) might do actually ends up being very important for human health.鈥澛
