Reducing the level of damaged cells to slow aging

Reducing the level of damaged cells to slow aging

Previous research published earlier this year in Nature Medicine 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.

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.

Of the 10 flavonoids tested, fisetin was the most potent senolytic. Acute or intermittent treatment of progeroid and old mice with fisetin reduced senescence markers in multiple tissues, consistent with a hit-andrun senolytic mechanism. Fisetin reduced senescence in a subset of cells in murine and human adipose tissue, demonstrating cell-type specificity.

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 the senior author. "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.

"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." the senior author said.

https://www.ebiomedicine.com/article/S2352-3964(18)30373-6/fulltext

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