Fisetin Benefits: The Underrated Flavonoid That May Help You Age Better

When it comes to promoting healthy aging, some compounds stand out from the crowd—and fisetin is one of them. Found in strawberries, apples, onions, and cucumbers, fisetin is a natural compound with antioxidant properties. It belongs to a class of polyphenols known as flavonoids, specifically referred to as the dietary flavonoid fisetin. But fisetin is more than just a dietary antioxidant.

In the last decade, scientists have uncovered experimental evidence that fisetin may play a unique role in slowing aging by clearing senescent cells, protecting against neurodegeneration, and reducing inflammation. These discoveries place fisetin at the forefront of research into senotherapeutics —compounds that target the cellular drivers of aging.

Let’s explore the science behind fisetin benefits and why this emerging bioactive is a featured ingredient in Vitality by Tally Health, our flagship formula designed to support healthy aging.

Fisetin is a naturally occurring flavonoid that has been studied for its antioxidant, anti-inflammatory, anti-cancer, and neuroprotective properties. While it’s found in many common fruits and vegetables, dietary intake is typically low—less than 0.4 mg per day in Western diets.

In animal and cell studies, fisetin has shown a remarkable ability to reduce markers of cellular senescence—cells that no longer divide and secrete harmful inflammatory molecules. Cell culture studies and research using human cell lines have been instrumental in uncovering fisetin's effects, particularly its impact on cancer cells and biological pathways. Animal studies serve as a foundation for our understanding of fisetin's biological activities and ability to target senescent cells. These so-called “zombie cells” accumulate with age and contribute to multiple chronic diseases.

Supplementing or focusing on fistein-rich foods (such as strawberries, red apples, and persimmons) are a great way to capture the health benefits of fisetin. Beneficial effects of fisetin include: preventing cellular senescence, cancer prevention, and improved skin health.

One of the most exciting fisetin benefits is its ability to act as a senolytic —a compound that selectively removes senescent cells from the body. Fisetin acts by destroying senescent cells, which helps to promote longevity by reducing the burden of these aging cells. Senescent cells are a hallmark of aging, implicated in conditions ranging from osteoarthritis to cardiovascular disease and frailty.

In a landmark study, fisetin treatment significantly reduced senescent cell burden in aged mice, improved tissue function, and extended both median and maximum lifespan—even when administered later in life. These findings have sparked a surge of interest in fisetin as a potential anti-aging therapeutic.

🧪 Fisetin is now being tested in multiple human clinical trials for its senolytic properties, including studies in osteoarthritis and frailty in older adults.

Fisetin also exerts protective effects in the brain. It crosses the blood-brain barrier and has demonstrated antioxidant, anti-inflammatory, and neurotrophic effects in animal models of Alzheimer’s, Parkinson’s, and other neurodegenerative diseases, as well as stroke.

In rodents, fisetin improves memory, reduces amyloid plaque formation, and enhances long-term potentiation—a process essential for learning and memory. It also supports mitochondrial function and reduces neuroinflammation, both of which are central to age-related cognitive decline.

Aging is associated with inflammaging —a chronic, low-grade inflammatory state that drives many age-related diseases. Fisetin helps curb this process by modulating pro-inflammatory cytokines like TNF-α, IL-6, and IL-1β and inhibiting nuclear factor kappa B (NF-κB), a master regulator of inflammation.

It also influences immune cell function, helping to shift the immune system away from an overactive, inflammatory state toward a more balanced and effective defense system—something that becomes increasingly important with age. Additionally, fisetin may affect mast cells, which are involved in inflammation, immune responses, and can contribute to the tumor microenvironment.

Fisetin is a potent scavenger of free radicals, specifically reactive oxygen species (ROS), and supports the activity of endogenous antioxidant enzymes like superoxide dismutase (SOD), catalase, and glutathione peroxidase. Fisetin helps prevent the decreased expression of these antioxidant enzymes, thereby enhancing cellular defense mechanisms. These enzymes are essential for protecting cells and mitochondria from oxidative damage, a major contributor to cellular aging and chronic disease. Additionally, fisetin's antioxidant effects support healthy cellular metabolism by protecting mitochondria from oxidative damage.

Emerging studies show that fisetin may improve insulin sensitivity, reduce triglycerides, and protect blood vessels by reducing oxidative stress and inflammation in endothelial cells. These effects may help reduce the risk of metabolic syndrome and cardiovascular disease—two of the biggest threats to healthspan.

Fisetin is a naturally occurring flavonoid found in a variety of fruits and vegetables. The foods richest in fisetin include:

• Strawberries (the highest known source)

• Apples

• Persimmons

• Onions

• Grapes

• Cucumbers

• Kiwis

While these are all healthy, antioxidant-rich choices, here’s the catch: you’d have to eat pounds of strawberries or dozens of apples per day to reach the fisetin levels used in most scientific studies that report senolytic or cognitive benefits.

That’s why fisetin supplements have gained interest: they provide a concentrated dose that would be very difficult to get through diet alone—without the added sugar or calories. For those looking to support cellular health, supplementing with clinically studied amounts of fisetin offers a more effective approach.

While fisetin is found in certain fruits and vegetables, the therapeutic doses used in clinical and preclinical studies are much higher than can be obtained from diet alone.

That’s why Vitality by Tally Health includes a clinically studied dose of fisetin, paired with other science-backed ingredients that support healthy aging by targeting multiple cellular pathways.