Scientists have developed genetically modified mice that could accelerate research into aging.
Researchers from Washington State University have engineered mice that may help speed up anti-aging studies.
Worldwide, scientists are striving to understand how to prolong human life at the cellular level, where aging occurs gradually as telomeres—the protective caps on the ends of chromosomes—shorten. These telomeres act like the tips of shoelaces, preventing chromosomes from unraveling. As they shorten over time, cells lose the ability to divide effectively, leading to deterioration and eventual cell death.
However, examining telomeres within human cells has proven difficult for researchers.
Recently, a team from WSU made a breakthrough published in the journal Nature Communications, which has opened possibilities for using these genetically modified mice.
Under the guidance of Professor Jiyue Zhu from the WSU College of Pharmacy and Pharmaceutical Sciences, the team has engineered mice with telomeres that closely resemble those of humans. This allows for the investigation of aging processes as they occur in humans and their organs, since typical mice possess telomeres that can be up to 10 times longer than those found in humans.
“This is the first mouse model that truly mimics human telomeres because telomerase is not present in adult tissues in this model,” Zhu stated. “Our research shows they have human-like telomeres. Our next step is to study how these mice age.”
Known as HuT mice—short for humanized telomeres—they are facilitating Zhu’s team in advancing several research initiatives. Major interests include understanding how shorter telomeres may decrease cancer risk and impact human lifespan, as well as investigating methods to extend the health span—the portion of life that is free from diseases associated with aging.
This research could have important implications for future drug development and treatments. In the long run, it may lead to anti-aging strategies aimed at activating cells to protect telomeres, possibly extending lifespans. Zhu emphasized that many diseases begin at the cellular level, making it a focal point for drug targeting.
Telomerase levels are critical since cancer cells divide quickly and require substantial telomerase amounts to sustain their telomeres. “One of our objectives is to decrease telomerase expression in cancer cells, which is a major research focus,” Zhu mentioned.
The mouse model enables a variety of aging studies, he explained. One collaborator, Christopher Davis from the WSU Elson S. Floyd College of Medicine, investigates the effects of sleep on human health. This team will utilize HuT mice to examine how sleep deprivation and various life stresses influence telomere maintenance and aging.
Zhu began his investigation into telomeres in the mid-1990s under the guidance of Nobel laureates Elizabeth Blackburn and J. Michael Bishop, who made significant contributions in understanding telomeres and cancer. He has been with WSU since 2014.
The creation of HuT mice started a decade ago when Zhu and his colleagues enhanced their knowledge of telomere regulation in humans and its differences from that in other animals. Previously, studies on how telomeres affected human aging could only be conducted using isolated human cells in a laboratory setting. “This mouse model is different because it allows us to witness the aging process within a complete organism,” Zhu explained. “Mice share many similarities with humans in terms of organ structure, genes, and genetic makeup.”
Zhu expressed hope that the WSU team will eventually share the mice with other research groups to further studies on aging, human longevity, and cancer. “There are thousands studying aging and cancer, and we believe this new mouse model will be a valuable asset for scientists around the globe to investigate these aspects.”
Zhu has secured $5 million in grants to advance the development of the mouse model that mimics human aging processes, as well as research into cancer ramifications. The funding includes grants from the National Institute on Aging, National Institute of General Medical Sciences, and the U.S. Department of Defense, the last of which will explore how telomere length affects melanoma cells.
