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[TEST] Making an Impact: Research identifies potential role of ‘junk DNA’ sequence in aging, cancer

Making an Impact header

Research identifies potential role of ‘junk DNA’ sequence in aging, cancer

 

We don’t often think about ourselves this way, but our bodies are made up of trillions of living cells. We age as our cells age, which happens when those cells eventually stop replicating and dividing. Scientists have long known that our genes influence how our cells age and how long we live, but how that works exactly remains unclear. Findings from a new study led by researchers at Washington State University have solved a small piece of that puzzle, bringing scientists one step closer to solving the mystery of aging.

A research team headed by Jiyue Zhu, a professor in the College of Pharmacy and Pharmaceutical Sciences, recently identified a DNA region known as VNTR2-1 that appears to drive the activity of the telomerase gene, which has been shown to prevent aging in certain types of cells. The study was published in the journal Proceedings of the National Academy of Sciences (PNAS).

Aging researcher Jiyue zhu talks to members of his research team inside his laboratory on the WSU Health Sciences Spokane campus.
Jiyue Zhu (second from left) talks to members of his research team inside his laboratory on the WSU Health Sciences Spokane campus, including Ken Porter (far left), Sean Mcgranaghan (center), Fan Zhang (second from right), and Jinlong Zhang (far right).

The telomerase gene controls the activity of the telomerase enzyme, which helps produce telomeres, the caps at the end of each strand of DNA that protect the chromosomes within our cells. In normal cells, the length of telomeres gets a little bit shorter every time cells duplicate their DNA before they divide. When telomeres get too short, cells can no longer reproduce, causing them to age and die. However, in certain cell types—including reproductive cells and cancer cells—the activity of the telomerase gene ensures that telomeres are reset to the same length when DNA is copied. This is essentially what restarts the aging clock in new offspring but is also the reason why cancer cells can continue to multiply and form tumors.

Knowing how the telomerase gene is regulated and activated and why it is only active in certain types of cells could someday be the key to understanding how we age, as well as how to stop the spread of cancer. That is why Zhu has focused the past 20 years of his career as a scientist solely on the study of this gene.

Junk no more

Zhu said that his team’s latest finding that VNTR2-1 helps to drive the activity of the telomerase gene is especially notable because of the type of DNA sequence it represents.

“Almost 50 percent of our genome consists of repetitive DNA that does not code for protein,” Zhu said. “These DNA sequences tend to be considered as ‘junk DNA’ or dark matters in our genome, and they are difficult to study. Our study describes that one of those units actually has a function in that it enhances the activity of the telomerase gene.”

Their finding is based on a series of experiments that found that deleting the DNA sequence from cancer cells—both in a human cell line and in mice—caused telomeres to shorten, cells to age, and tumors to stop growing. Subsequently, they conducted a study that looked at the length of the sequence in DNA samples taken from Caucasian and African American centenarians and control participants in the Georgia Centenarian Study, a study that followed a group of people aged 100 or above between 1988 and 2008. The researchers found that the length of the sequence ranged from as short as 53 repeats—or copies—of the DNA to as long as 160 repeats.

“It varies a lot, and our study actually shows that the telomerase gene is more active in people with a longer sequence,” Zhu said.

Since very short sequences were found only in African Americans participants, they looked more closely at that group and found that there were relatively few centenarians with a short VNTR2-1 sequence as compared to control participants. However, Zhu said it was worth noting that having a shorter sequence does not necessarily mean your lifespan will be shorter, because it means the telomerase gene is less active and your telomere length may be shorter, which could make you less likely to develop cancer.

“Our findings are telling us that this VNTR2-1 sequence contributes to the genetic diversity of how we age and how we get cancer,” Zhu said. “We know that oncogenes—or cancer genes—and tumor suppressor genes don’t account for all the reasons why we get cancer. Our research shows that the picture is a lot more complicated than a mutation of an oncogene and makes a strong case for expanding our research to look more closely at this so-called junk DNA.”

Next step

Zhu noted that since African Americans have been in the United States for generations, many of them have Caucasian ancestors from whom they may have inherited some of this sequence. So as a next step, he and his team hope to be able to study the sequence in an African population.

In addition to Zhu, authors on the paper include co-first authors Tao Xu and De Cheng and others at Washington State University, as well as their collaborators at Northeast Forestry University in China; Pennsylvania State University; and North Carolina State University.

Funding for this study came from the National Institutes of Health’s National Institute of General Medical Sciences, the Melanoma Research Alliance, and the Health Sciences and Services Authority of Spokane County.

 

 

Researcher on the Rise: Q&A with Cassandra Nikolaus

Researcher on the Rise header

Q&A with Cassandra Nikolaus

A research assistant professor in the Elson S. Floyd College of Medicine, Cassandra Nikolaus conducts research focused on food security within the WSU Institute for Research and Education to Advance Community Health (IREACH). Her journey into academia took her from her local community college in Everett, Washington, to Central Washington University, where she studied nutrition and dietetics and became the first in her family to earn a bachelor’s degree. She then completed her graduate studies at the University of Illinois Urbana-Champaign before accepting a position as a postdoctoral research associate at WSU in 2019.

What drew you to WSU?
I was particularly interested in working for WSU as the state’s land grant institution, with the teaching, research, and Extension arms complementing each other. I believe that the knowledge generated by researchers should not just be in journals and only benefit other academics. Bringing that research to practice is a really important part of my ethos. Besides that, my mentor Ka’imi Sinclair [an associate professor within IREACH Ed.] has been a great advocate for all of my interests and has really taken me under her wing to ensure that I am successful here. I am really excited to be a part of WSU.

What fueled your passion to do research on food security?
As the youngest of four children raised by a single mother, I experienced food insecurity growing up. However, it was not until I was at Central Washington University as a student who was actively receiving SNAP benefits to supplement my food budget that I even learned the terminology for it. I was really interested in helping people eat healthfully despite barriers such as income or rural access issues. Having caught the research bug, I realized that by doing research in the area of food security I could make a difference for households and families experiencing some of the same challenges I had lived through.

How common is food insecurity and what are the consequences?
Though it varies based on the state of the economy, the U.S. Department of Ag riculture estimates that about one in nine U.S. households experience food insecurity. Food insecurity is related to both poor physical and mental health, including increased risk of depression, diabetes, and obesity.

What are some of the challenges your research addresses?
About one in every four households led by American Indians or Alaska Natives experiences food insecurity. Yet in the annual report published by the U.S. Department of Agriculture on household food security, American Indians and Alaska Natives are lumped together with other racial and ethnic groups in this “Other” category. This practice disregards the vast differences between these groups and makes American Indians and Alaska Natives invisible in our larger political discussions of solutions to address food insecurity. It is why a lot of my work has been looking to increase what we know about food insecurity among American Indians and Alaska Natives to advocate for their continued disaggregation in reports like this. However, it is important to recognize that even when broken separately this category of American Indians and Alaska Natives is still extremely diverse, representing more than 600 recognized tribes spread out across both rural and urban areas throughout the U.S.

You recently received a three-year mentored career development award from the Institute for Translational Health Sciences. What does that grant entail?
Healthcare providers increasingly recognize food security as playing an important role in health, but whether or not they are screening for it and implementing it into their care practice is still not well understood. This new grant will help me gain the skills to complete a research project that looks at the use and implementation of food security screening in more than 600 community health centers nationwide based on electronic health records maintained by OCHIN, a national nonprofit health IT organization. In collaboration with Dr. Rachel Gold, lead research scientist at OCHIN, I will be looking for variations in screening practices across clinics, providers, patients, and types of visits.

What advantages does food security screening in healthcare settings offer?
Integrating food security screening into the healthcare system ensures the proximity of food security information to robust health information. It allows healthcare providers to consider patients’ food insecurity when making care recommendations and refer patients to external services for food assistance. It can also help them clearly see whether alleviating food insecurity has an impact on their patients’ health. Plus, in pediatric care it can help catch food insecurity sooner. That is important, because we know that food insecurity experiences in childhood or young adulthood can potentially have ramifications later in life.

What other projects are you working on?
I am wrapping up a one-year pilot project in which I analyzed existing data to look at food insecurity in young adulthood and how it related to cardiometabolic health outcomes—such as glucose maintenance, body weight, and blood pressure—when study participants were assessed again in middle age.

I am also working on a two-year pilot project that looks at how food security relates to alcohol use among American Indian and Alaska Native parents and the social emotional development of their children. This is based on an existing data set that will allow me to see whether food insecurity predates problematic alcohol use or vice versa.

Finally, I will be evaluating how a set of food security-related survey questions used as part of the annual National Health Interview Survey performs when we specifically analyze American Indian and Alaska Native respondents. The outcome could either help us build a case for disaggregating American Indian and Alaska Native-led households in the annual report from USDA or demonstrate the need to modify the survey questions to better account for food-related cultural practices and norms that are unique to this group.

What do you hope to accomplish with your research in the long term?
My real hope is that my research career will help bridge the gap between what we know and what we do about food insecurity in this country. I would love to see my work lead to new programs and policies to mitigate some of these long-term health outcomes of food insecurity and ultimately prevention of food insecurity experiences for individuals in the U.S. across the lifespan.

Making an Impact: Research identifies potential role of ‘junk DNA’ sequence in aging, cancer

Making an Impact header

Research identifies potential role of ‘junk DNA’ sequence in aging, cancer

 

We don’t often think about ourselves this way, but our bodies are made up of trillions of living cells. We age as our cells age, which happens when those cells eventually stop replicating and dividing. Scientists have long known that our genes influence how our cells age and how long we live, but how that works exactly remains unclear. Findings from a new study led by researchers at Washington State University have solved a small piece of that puzzle, bringing scientists one step closer to solving the mystery of aging.

A research team headed by Jiyue Zhu, a professor in the College of Pharmacy and Pharmaceutical Sciences, recently identified a DNA region known as VNTR2-1 that appears to drive the activity of the telomerase gene, which has been shown to prevent aging in certain types of cells. The study was published in the journal Proceedings of the National Academy of Sciences (PNAS).

Aging researcher Jiyue zhu talks to members of his research team inside his laboratory on the WSU Health Sciences Spokane campus.
Jiyue Zhu (second from left) talks to members of his research team inside his laboratory on the WSU Health Sciences Spokane campus, including Ken Porter (far left), Sean Mcgranaghan (center), Fan Zhang (second from right), and Jinlong Zhang (far right).

The telomerase gene controls the activity of the telomerase enzyme, which helps produce telomeres, the caps at the end of each strand of DNA that protect the chromosomes within our cells. In normal cells, the length of telomeres gets a little bit shorter every time cells duplicate their DNA before they divide. When telomeres get too short, cells can no longer reproduce, causing them to age and die. However, in certain cell types—including reproductive cells and cancer cells—the activity of the telomerase gene ensures that telomeres are reset to the same length when DNA is copied. This is essentially what restarts the aging clock in new offspring but is also the reason why cancer cells can continue to multiply and form tumors.

Knowing how the telomerase gene is regulated and activated and why it is only active in certain types of cells could someday be the key to understanding how we age, as well as how to stop the spread of cancer. That is why Zhu has focused the past 20 years of his career as a scientist solely on the study of this gene.

Junk no more

Zhu said that his team’s latest finding that VNTR2-1 helps to drive the activity of the telomerase gene is especially notable because of the type of DNA sequence it represents.

“Almost 50 percent of our genome consists of repetitive DNA that does not code for protein,” Zhu said. “These DNA sequences tend to be considered as ‘junk DNA’ or dark matters in our genome, and they are difficult to study. Our study describes that one of those units actually has a function in that it enhances the activity of the telomerase gene.”

Their finding is based on a series of experiments that found that deleting the DNA sequence from cancer cells—both in a human cell line and in mice—caused telomeres to shorten, cells to age, and tumors to stop growing. Subsequently, they conducted a study that looked at the length of the sequence in DNA samples taken from Caucasian and African American centenarians and control participants in the Georgia Centenarian Study, a study that followed a group of people aged 100 or above between 1988 and 2008. The researchers found that the length of the sequence ranged from as short as 53 repeats—or copies—of the DNA to as long as 160 repeats.

“It varies a lot, and our study actually shows that the telomerase gene is more active in people with a longer sequence,” Zhu said.

Since very short sequences were found only in African Americans participants, they looked more closely at that group and found that there were relatively few centenarians with a short VNTR2-1 sequence as compared to control participants. However, Zhu said it was worth noting that having a shorter sequence does not necessarily mean your lifespan will be shorter, because it means the telomerase gene is less active and your telomere length may be shorter, which could make you less likely to develop cancer.

“Our findings are telling us that this VNTR2-1 sequence contributes to the genetic diversity of how we age and how we get cancer,” Zhu said. “We know that oncogenes—or cancer genes—and tumor suppressor genes don’t account for all the reasons why we get cancer. Our research shows that the picture is a lot more complicated than a mutation of an oncogene and makes a strong case for expanding our research to look more closely at this so-called junk DNA.”

Next step

Zhu noted that since African Americans have been in the United States for generations, many of them have Caucasian ancestors from whom they may have inherited some of this sequence. So as a next step, he and his team hope to be able to study the sequence in an African population.

In addition to Zhu, authors on the paper include co-first authors Tao Xu and De Cheng and others at Washington State University, as well as their collaborators at Northeast Forestry University in China; Pennsylvania State University; and North Carolina State University.

Funding for this study came from the National Institutes of Health’s National Institute of General Medical Sciences, the Melanoma Research Alliance, and the Health Sciences and Services Authority of Spokane County.