Wednesday, October 3, 2018

Researchers Discover How to Slow Aging



Previous research published earlier this year in Nature Medicine involving University of Minnesota Medical School faculty Paul D. Robbins and Laura J. Niedernhofer and Mayo Clinic investigators James L. Kirkland and Tamara Tchkonia, showed it was possible to reduce the burden of damaged cells, termed senescent cells, and extend lifespan and improve health, even when treatment was initiated late in life. They now have shown that treatment of aged mice with the natural product Fisetin, found in many fruits and vegetables, also has significant positive effects on health and lifespan.

Laura J. Niedernhofer and Paul D. Robbins

Credit: University of Minnesota Medical School

As people age, they accumulate damaged cells. When the cells get to a certain level of damage they go through an aging process of their own, called cellular senescence. The cells also release inflammatory factors that tell the immune system to clear those damaged cells. A younger person’s immune system is healthy and is able to clear the damaged cells. But as people age, they aren’t cleared as effectively. Thus they begin to accumulate, cause low-level inflammation and release enzymes that can degrade the tissue.

Robbins and fellow researchers found a natural product, called Fisetin, reduces the level of these damaged cells in the body. They found this by treating mice towards the end of life with this compound and see improvement in health and lifespan. The paper, “Fisetin is a senotherapeutic that extends health and lifespan,” was recently published in EBioMedicine.

“These results suggest that we can extend the period of health, termed healthspan, even towards the end of life,” said Robbins. “But there are still many questions to address, including the right dosage, for example.”

One question they can now answer, however, is why haven’t they done this before? There were always key limitations when it came to figuring out how a drug will act on different tissues, different cells in an aging body. Researchers didn’t have a way to identify if a treatment was actually attacking the particular cells that are senescent, until now.

Under the guidance of Edgar Arriaga, a professor in the Department of Chemistry in the College of Science and Engineering at the University of Minnesota, the team used mass cytometry, or CyTOF, technology and applied it for the first time in aging research, which is unique to the University of Minnesota.

“In addition to showing that the drug works, this is the first demonstration that shows the effects of the drug on specific subsets of these damaged cells within a given tissue,” Robbins said.

Dr. Niedernhofer is the director and Dr. Robbins co-director of the Medical Discovery Team on Aging and the new Institute on the Biology of Aging and Metabolism (iBAM) at the University of Minnesota Medical School which are focusing on basic and translational research to identify novel and effective approaches to improve the health of the aging population.


Contacts and sources:
Krystle BarbourUniversity of Minnesota Medical School



Citation: Fisetin is a senotherapeutic that extends health and lifespan.
Matthew J. Yousefzadeh, Yi Zhu, Sara J. McGowan, Luise Angelini, Heike Fuhrmann-Stroissnigg, Ming Xu, Yuan Yuan Ling, Kendra I. Melos, Tamar Pirtskhalava, Christina L. Inman, Collin McGuckian, Erin A. Wade, Jonathon I. Kato, Diego Grassi, Mark Wentworth, Christin E. Burd, Edgar A. Arriaga, Warren L. Ladiges, Tamara Tchkonia, James L. Kirkland, Paul D. Robbins, Laura J. Niedernhofer. EBioMedicine, 2018; DOI: 10.1016/j.ebiom.2018.09.015



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