Fisetin: A Senolytic That Extends Life

Senolytics have been shown to improve health and extend lifespan in experimental models.

These compounds work by helping the body clear away old, damaged (senescent) cells to make way for new, healthy cells.

Fisetin, a flavonoid found in various plants, is one of the most powerful natural senolytics ever discovered.

Preclinical and some preliminary clinical studies suggest it may protect against age-related disorders,^1-15 slow certain aging processes, and promote longevity.^10,16

Old mice given fisetin had a nearly 10% increase in lifespan.¹⁷

One challenge has been that fisetin is rapidly metabolized in the digestive tract. This means very little is absorbed into the bloodstream.

But scientists have developed a way to overcome this problem by combining it with natural compounds from the fenugreek plant.

This novel formulation increased the bioavailability of fisetin by as much as 25 times.¹⁸

What Is Fisetin?

Fisetin is a flavonoid that has gained popularity in recent years due to its potential health benefits.

It is found in small amounts in many fruits and vegetables, including strawberries, apples, persimmons, grapes, and onions.

Fisetin shares some of the anti-aging, disease-fighting properties of other polyphenols. Yet it stands out for its remarkable potency as a senolytic. ¹⁷

Improved Bioavailability

There’s long been a problem with oral fisetin. Soon after ingestion, it is rapidly metabolized in the gut, making it much less effective.

Scientists have now solved this problem by combining fisetin with a form of fiber known as galactomannans, isolated from the spice fenugreek.

This novel formulation has been shown to increase the bioavailability (absorption) of fisetin by as much as 25 times, which may greatly improve its impact on health and longevity.¹⁸

A Powerful Senolytic

Senescent cells are aged cells that stop functioning properly and can cause damage to surrounding tissues. They lose the ability to grow or divide, and they refuse to die off, earning them the name “zombie cells.”

These senescent cells spew out compounds that incite harmful systemic inflammation inflicting even more damage.^19,20

Senescent cells are a major driver of age-related disease and dysfunction. They even accelerate the aging process itself.

Senolytics are compounds with the ability to destroy senescent cells. They hold great promise in the fight against aging and age-related disease, slowing or even reversing the aging process.^16,17,21,22

One of the first senolytics discovered was another polyphenol, quercetin, which works effectively when coupled with a chemotherapy drug, dasatinib.

Fisetin is a more powerful senolytic than quercetin. And it works on its own, without the potential side effects of cancer drugs.

A cell study published in the journal Aging showed that it eliminated about 70% of senescent cells—while doing no harm to healthy, normal human cells. ²²

Another study tested 10 plant-derived compounds, including quercetin, head-to-head. Fisetin was the most effective at eliminating senescent cells, both in cell cultures and in an animal model.¹⁷

These findings suggest fisetin may be an effective weapon in the fight against aging.

There are a number of human trials of fisetin currently in progress.²³ But an animal study has already shown striking results.

When mice that were the human equivalent of 75 years of age were given fisetin, they lived an average of 2.5 months longer. That’s close to a 10% increase in lifespan.¹⁷

Fighting Oxidative Stress and Inflammation

Fisetin promotes longevity in several other ways. Oxidative stress and chronic inflammation accelerate aging processes and increase risk for chronic diseases.

Fisetin is an antioxidant and anti-inflammatory. By scavenging harmful free radicals, it prevents the damage they do to DNA, proteins, and other cellular components.²⁴

It reduces inflammation by shutting off pathways that promote it, and by reducing the production of pro-inflammatory compounds.¹⁰

Mimicking Caloric Restriction

Reducing food intake through a calorie-restricted diet has been shown to slow aging, extend lifespan, and improve resistance to disease. ²⁵

Research has identified the cellular pathways that are affected by such a diet. Among other benefits, caloric restriction:²⁶

• Reduces the activity of mTOR, a protein linked to aging, weight gain, and chronic disease,
• Boosts the function of sirtuins, proteins that regulate cellular health,
• Increases the activity of AMPK, an enzyme that regulates metabolism, and
• Promotes autophagy, cellular “housekeeping.”

Researchers have found that fisetin has a similar effect on every one of these pathways, mimicking the effects of caloric restriction.^10,16,27,28

For example, sirtuin proteins shield cells from damage and help keep them in peak form. But sirtuin function diminishes with age, leading to increased susceptibility to disease and rapid aging.^29,30

AMPK activity also declines with age, increasing risk for deteriorating metabolic function, obesity, diabetes, and more.³¹

Several preclinical studies have shown that fisetin increases sirtuin function and AMPK activity.^32-34 This protects cells and keeps them on a youthful and healthy path.

Protecting the Heart

Fisetin not only has the ability to extend lifespan in preclinical models, it may also reduce the risk for many of the most common chronic illnesses.

Heart disease remains the leading cause of death in the U.S. Most common forms of heart disease are due to inadequate flow of blood, oxygen, and nutrients to the heart, which can lead to a heart attack.

Over the last two years, studies have demonstrated that fisetin can protect the heart from injury. Even after heart attack models, heart cells fare better when fisetin is present.

In one recent study published in the journal Nature, rat heart cells starved for nutrients and oxygen were protected by fisetin, preventing cell death.³⁵

And in animal models of heart attack, the extent of heart damage was reduced when treated with fisetin, preserving better heart function. ^36,37

In humans who suffer a heart attack, an arrhythmia (abnormal heart rhythm) can often develop.³⁸ In an animal study, fisetin intake after a heart attack significantly reduced the risk of atrial fibrillation, a common arrhythmia that increases the likelihood of stroke or heart failure.³⁹

Preventing Obesity and Metabolic Disorders

Fisetin may also help to prevent obesity and common metabolic disorders, like type II diabetes.

Obesity predisposes people to higher rates of cardiovascular disease as well as cancer, dementia, and many other conditions.

By increasing activity of AMPK and decreasing activity of mTOR, fisetin may reduce weight gain and protect against related disorders. Even in mice fed a high-fat diet, fisetin prevented weight gain while protecting the liver, heart, and other organs.^5,10,40,41

Rodent models of diabetes find that fisetin reduces body weight and improves glucose control and insulin sensitivity.^4,12,40-42

Having better glucose control can protect against many of the diabetic complications, like kidney disease, eye disease, and neurological disorders.

Life Extension has long suggested the importance of keeping fasting blood glucose between 70-85 mg/dL, which is challenging for most aging people to accomplish. Fisetin may offer a solution to stubbornly high glucose levels.

Fighting Cancer

As an anti-inflammatory, fisetin may lower the risk of developing cancer. ^43-46 But fisetin’s anti-cancer activity goes even further.

Two recent preclinical studies have shown fisetin to be effective in controlling even some of the most aggressive forms of cancer.

In one, scientists investigated the impact of fisetin on human glioblastoma cells.⁴⁷ Glioblastoma, a malignant brain tumor, is one of the most invasive and rapidly growing forms of cancer. Even with surgery and chemotherapy, it is usually impossible to control.

Fisetin treatment significantly reduced the growth of glioblastoma cells and even caused them to die off. When directly compared to a chemotherapy drug called carmustine, fisetin killed cancer cells at lower doses.

In another recent study, fisetin was effective against several cell lines of triple negative breast cancer. This aggressive form of breast cancer is highly resistant to most medical treatments.⁴⁸

In several other studies, fisetin prevented cancer migration and growth while reducing inflammation, enhancing autophagy, and inciting cancer cell death.^11,49-55

Fisetin may one day be considered as an adjuvant nutritional approach by progressive oncologists.

Brain Benefits

Fisetin has been demonstrated to be neuroprotective in animal models of Alzheimer’s disease, Parkinson’s disease, ALS (amyotrophic lateral sclerosis), and others.^1-3,8-10,15

In a 2019 clinical study, fisetin was found to help in the treatment of a stroke.

Strokes typically occur suddenly, without warning, and can lead to permanent loss of brain function. The most effective medical treatments dissolve or remove the blood clot blocking blood flow to the brain.

But the best chance for success comes when treatment is initiated within three hours of the onset of symptoms.⁵⁶

Fisetin has been shown to extend this treatment window to five hours.¹³ While this two-hour extension may not seem huge, it can dramatically increase the number of stroke patients who benefit from clot dissolving and/or clot removing (endovascular thrombectomy) brain-saving therapy.

Summary

Fisetin is a flavonoid found in several fruits and vegetables, such as strawberries and apples.

Recent research has found fisetin to be one of the most effective senolytic compounds yet discovered among plant polyphenols. By helping to remove dysfunctional senescent cells, fisetin may increase longevity and lower risk for disease.

In mice, fisetin intake increased lifespan by nearly 10%, even when started late in life.

Combining fisetin with compounds isolated from fenugreek allows more fisetin to be absorbed and distributed in the body to aging tissues that can benefit from its health-promoting actions.

If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.

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