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Natural Product (Fisetin) Found to Extend Healthspan in Animal Model; Mass Spec Technique Shows Effects on Specific Subsets of Cells

Previous research published earlier this year in Nature Medicine (https://www.nature.com/articles/s41591-018-0092-9) involving University of Minnesota Medical School faculty Dr. Paul D. Robbins and Dr. Laura J. Niedernhofer and Mayo Clinic investigators Dr. James L. Kirkland and Dr. 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 (image), found in many fruits and vegetables, also has significant positive effects on health and lifespan. 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, these damaged cells aren't cleared as effectively. Thus, they begin to accumulate, cause low level inflammation, and release enzymes that can degrade tissue. Dr. Robbins and fellow researchers found that 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 seeing improvement in health and lifespan. The open-access article, "Fisetin Is a Senotherapeutic That Extends Health and Lifespan," was published on September 29, 2018 in EBioMedicine. "These results suggest that we can extend the period of health, termed healthspan, even towards the end of life," said Dr. Robbins. "But there are still many questions to address, including the right dosage, for example."

One question researchers 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 Dr. 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." Dr. 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.

[Press release] [EBioMedicine article]