Fisetin is a Natural Senolytic

Senolytics are pharmaceuticals or nutraceuticals with unique abilities to remove dangerous senescent zombie cells.

Senescent Zombie Cells and Fisten

Fisetin is a naturally occurring flavonoid family found most abundantly in strawberries.

The researchers at the Scripps Institute compared fisetin against other powerful natural compounds, including resveratrol, luteolin, rutin, EGCG from green tea, curcumin, myricetin, apigenin, among others. This study revealed fisetin to be far away the most effective of these compounds in removing toxic senescent cells.

In old mice, fisetin reduced senescence markers in multiple tissues (also in human tissue). Feeding fisetin to wild-type mice late in life restored tissue homeostasis, reduced age-related disease and extended lifespan.

These two mice are litter mates; the only difference is that the mouse on the left has aged normally while the mouse on the right has had its senescent cells removed and appears considerably more healthy.

University of Minnesota Medical School faculty members Dr. Paul D. Robbins and Dr. Laura J. Niedernhofer, along with Mayo Clinic investigators Dr. James L. Kirkland and Dr.Tamara Tchkonia published a breakthrough study…

“Fisetin is a senotherapeutic that extends health and lifespan” in the journal EBioMedicine:

During their study, they discovered fisetin was able to remove senescent cells from aged mice, which improved their health and lifespan.

The researchers found that getting rid of only 30% of senescent cells is enough to have a major impact on health and longevity.

Dr. Niedernhofer states, “Senescent cells aren’t like cancer where to cure it, you have to kill every cancer cell.”

Fisetin, the natural flavonoid, removed 25 to 50% of senescent cells depending on the organ.

These mice fed fisetin late in life (the equivalent of 75 years in humans) lived 10-15% longer than the mice that didn’t get the fisetin. This represents a 50% increase in their remaining lifespan.

The researchers continued, “This fisetin is a natural compound present in small amounts many fruits and vegetables. Importantly, no adverse effects of fisetin have been reported, even when given at high doses.”

“Thus, our results suggest that supplementation or even intermittent treatment with this safe, natural product could improve healthy aging, even in elderly individuals.”

The researchers of this study have confirmed that fisetin is targeting and destroying senescent cells rather than simply blocking their signals or altering them in some beneficial way but not removing them.

“Nutraceuticals can be used to mimic the anti‐aging effects of longevity drugs without adverse effects.”

~ Alex Zhavoronkov, Ph.D. / Editor, Cell Aging

(credit: Salk Institute For Biological Studies)

Natural plant compound prevents Alzheimer’s disease in mice

A daily dose of the antioxidant FISETIN keeps mice—even those with genetic mutations linked to Alzheimer’s—from experiencing memory and learning deficits as they age.

“We had already shown that in normal animals, fisetin can improve memory,” says Pamela Maher, Ph.D, a senior staff scientist in Salk’s Cellular Neurobiology Laboratory, who led the new study. “What we showed here is that it also can have an effect on animals prone to Alzheimer’s.”

More than a decade ago, Maher discovered that fisetin helps protect neurons in the brain from the effects of aging. She and her colleagues have since—in both isolated cell cultures and mouse studies—probed how the compound has both antioxidant and anti-inflammatory effects on cells in the brain.

Most recently, they found that fisetin turns on a cellular pathway known to be involved in memory.

So Maher—who works with Dave Schubert, Ph.D., the head of the Cellular Neurobiology Lab—turned to a strain of mice that have mutations in two genes linked to Alzheimer’s disease. The researchers took subset of these mice and, when they were only three months old, began adding fisetin to their food.

As the mice aged, the researchers tested their memory and learning skills with water mazes. By nine months of age, mice that hadn’t received fisetin began performing more poorly in the mazes. Mice that had gotten a daily dose of fisetin, however, performed as well as normal mice, at both nine months and a year old.

“Even as the disease would have been progressing, the fisetin was able to continue preventing symptoms,” Maher says.