SPOKANE, Wash. — Washington State University scientists have created genetically-engineered mice that could help accelerate anti-aging research.
Globally, scientists are working to unlock the secrets of extending human lifespan at the cellular level, where aging occurs gradually due to the shortening of telomeres–the protective caps at the ends of chromosomes that function like shoelace tips to prevent unraveling. As telomeres shorten over time, cells lose their ability to divide for healthy growth, and some eventually begin to die.
But research studying these telomeres at the cellular level has been challenging in humans.
Now, a discovery by a WSU research team published today in the journal Nature Communications has opened the door to using the genetically engineered mice.
Led by WSU College of Pharmacy and Pharmaceutical Sciences Professor Jiyue Zhu, the research team has developed mice that have human-like short telomeres, enabling the study of cellular aging as it occurs in the human body and within organs. Normally mice have telomeres that are up to 10 times longer than humans.
"This is the first mouse model with truly humanized telomeres because telomerase isn't expressed in adult tissues in this model," Zhu said. "Our paper demonstrates that they exhibit human-like telomeres. Now, we aim to observe how these mice age."
Called HuT mice for their humanized telomeres, they are enabling Zhu's team to advance multiple research projects. Key areas of focus include studying how short telomeres reduce the likelihood of developing cancer and influence human lifespan, as well as exploring strategies to extend individuals' health span– the period of life free from age-related diseases.
The work has significant implications for the development of future drugs and treatments. In the long term it may pave the way for anti-aging strategies aimed to activating cells to protect telomeres, and potentially extend lifespans. Zhu noted that many diseases originate at the cellular level, so targeting drugs there is a common strategy.
Telomerase levels are crucial because cancer cells divide rapidly and need high amounts of telomerase to maintain their telomeres. "One of our goals is to reduce telomerase expression in cancer cells, and this is an active area of research."
The mouse model allows for multiple aging studies, Zhu said. One of his collaborators, WSU Elson S. Floyd College of Medicine researcher Christopher Davis, studies how sleep impacts human health. The group will use HuT mice to see how the stress of sleep deprivation and other life stresses affect telomere regulation and aging.
Zhu began telomere studies in the mid-1990s under researchers and Nobel Prize winners Elizabeth Blackburn and J. Michael Bishop, both pioneers in understanding telomeres and cancer. Zhu joined WSU in 2014.
The development of HuT mice began 10 years ago, when he and other researchers gained a deeper understanding of telomere regulation in humans and how it differs from animals. Previously, how telomeres regulated the human aging process could only be studied using isolated human cells in a petri dish. "This mouse model is quite different, as it allows us to observe the aging process in a whole organism," Zhu said. "Mice are similar to humans in terms of organ structure, genes, and genetic makeup."
Zhu said the WSU team hopes to eventually share the mice with other research teams to help advance studies on aging, human longevity, and cancer. "There are thousands of people studying aging and cancer, and we believe the new mouse model provides a valuable tool for scientists worldwide to explore these processes."
Zhu received $5 million in grants for studies to further develop the mouse model that simulates human replicative aging as well as to research cancer implications. The funding includes grants from the National Institute on Aging, National Institute of General Medical Sciences and the U.S. Department of Defense, with the latter to study how telomere length affects melanoma cancer cells.
