Researchers nationwide, including a team from The University of Texas Health Science Center at San Antonio, are embarking on a massive effort to learn the locations and roles of senescent “zombie” cells in humans. The health science center is part of a multi-institution group selected by the National Institutes of Health and the NIH Common Fund to map the cells’ presence in human kidney, fat, pancreas and placenta tissues.
UT Health Science Center San Antonio is a collaborating center in a $13.5 million NIH award (U54 AG075941) titled the KAPP-Sen Tissue Mapping Collaborative. KAPP is short for kidney, adipose (fat), pancreas and placenta. Coordinating centers are the UConn Center on Aging at UConn Health and Jackson Laboratory for Genomic Medicine in Farmington, Conn. Other research collaborators are Brigham and Women’s Hospital and the Joslin Diabetes Center in Boston and the Mayo Clinic in Rochester, Minn.
Nicolas Musi, MD, professor of medicine and director of the Sam and Ann Barshop Institute for Longevity and Aging Studies at the health science center, leads the biospecimen core of the project.
In an altered state, like zombies
Although likened to zombies, senescent cells are still alive. However, they no longer divide and they emit substances that may be harmful or beneficial depending on the situation. The cells are implicated in aging and many age-related diseases.
“We’ve learned that these nondividing cells produce a number of inflammatory substances,” Dr. Musi said. “There is also some evidence, mainly in studies in animals, that removing these cells with drugs can improve diseases of aging.
“But these cells may also play important roles in normal physiology, so we need to learn where they are, in what tissues, in what amounts, how they change with age, how they differ between sexes and ethnicities, and what their function is,” he said.
Sifting human samples for valuable information
Tissue procurement will be from UT Health Science Center San Antonio and beyond. “Within our university is a very strong collaboration between the UT Health San Antonio Transplant Center, led by Dr. Francisco Cigarroa, and the Barshop Institute,” Dr. Musi said. “Dr. Cigarroa and Dr. Seiji Yamaguchi will assist with providing healthy kidney tissue and healthy fat tissue from organ donors, as well as pancreatic tissue from expired donors who received care in the organ-preserving unit called the Center for Life in University Hospital. Placental tissue will come from collaborators at the Mayo Clinic.”
Part of a larger NIH initiative
Fat cells, blood cells, vascular cells and other types of cells can become senescent. A substantial portion of the body is made up of the zombie cells, and their numbers increase with age. But scientists don’t know the scope, which the Cellular Senescence Network: Tissue Mapping Centers Initiative of NIH seeks to change. KAPP-Sen is a part of the overall initiative.
Interest is increasing. There is evidence that the senescent cells accumulate in the brain. Accumulation in fat tissue has been related to obesity and diabetes in rodents. Zombie cells are also being associated with cardiovascular disease.
But, paradoxically, they may promote vital processes such as wound repair and labor.
“Are all of them inflammatory or are some less harmful?” Dr. Musi asked. “For example, it seems that these cells are very important in pregnancy. Their presence in the placenta and umbilical cord may be important for normal labor. Understanding the normal situation will be very important to guide future therapies in humans.”
Barshop Institute’s multiple designations
The new NIH U54 grant adds another jewel in the crown of the Barshop Institute, which is one of America’s premier aging research centers. The Barshop Institute now includes:
- Two National Institute on Aging P30 centers, the Nathan Shock Center of Excellence in the Basic Biology of Aging and the Claude D. Pepper Older Americans Independence Center.
- A National Institute on Aging U01 grant for the Interventions Testing Program.
- A National Institute on Aging T32 Institutional Training Grant.
- An NIH Common Fund U01 grant called MoTrPAC (Molecular Transducers of Physical Activity Consortium).
- The San Antonio Geriatric Research, Education and Clinical Center in collaboration with the South Texas Veterans Health Care System.