Fisetin is a type of flavonoid found in a range of fruits and vegetables, including strawberries, apples, persimmon, grapes, onions, and cucumbers. Flavonoids are nutrients found in plants that provide different health benefits when consumed. To date, various cell and animal studies show that fisetin elicits a range of positive health effects, including anti-inflammatory and antioxidant properties and the potential to support longevity. Let’s examine fisetin’s properties and its role as a health-boosting longevity compound. 


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How fisetin improves longevity on a cellular level 

fisetin senolytic

Researchers have been studying fisetin for years for its capacity to act as an antioxidant and reduce inflammation in the body. However, newer research has demonstrated that fisetin exerts powerful effects on different pathways in the body, especially ones related to longevity. We’ll explore the following three characteristics illustrating fisetin’s ability to improve both health- and lifespan: 

  1. Senolytic activity: its ability to destroy old and damaged cells, called “senescent cells”, that can accelerate the aging process.
  2. Mimics calorie restriction: fisetin has similar effects as calorie restriction, a practice that is strongly associated with many pro-longevity effects. 
  3. Anti-inflammatory and antioxidant properties: fisetin reduces inflammation and may increase glutathione activity. Glutathione is known as the “master antioxidant” in humans.  

Much of the research on fisetin’s effect on aging and longevity has occurred only within the last few years, in mice models, but shows promising results. Mice exposed to fisetin lived 10% longer and experienced fewer age-related issues compared to the control group.[1] Fortunately, these findings have led to the development of many clinical trials examining the direct effects of fisetin supplementation on age-related dysfunction in humans.[2] 


Fisetin’s impact as a senolytic 

Scientists attribute cell senescence as one of the hallmarks of aging. Senescent cells are aged cells with damaged DNA, which causes them to stop functioning properly. Often referred to as “zombie cells,” these cells do not die, leading them to accumulate and inflame surrounding cells and tissues. Cellular senescence can lead to the gradual deterioration of an organism and accelerate many age-related diseases.

Senolytics, on the other hand, are compounds that can destroy senescent cells, helping to prevent age-related disease and even alleviate those that may have already developed. Studies show that fisetin is a very powerful senolytic, especially compared to other flavonoids. This study from the journal Aging found that fisetin significantly removed senescent cells when applied to human umbilical vein endothelial cells. Fisetin has also been tested compared to other plant-derived senolytics, like quercetin (a compound found in high amounts in onions). Out of the ten compounds tested, fisetin was the most effective at destroying senescent cells in both animal models and human cell cultures.[3] 

fisetin research


How fisetin mimics calorie restriction 

Calorie restriction has shown to have many longevity effects, including extending lifespan and reducing age-related diseases.[4] It does this through different mechanisms, including activating sirtuins (proteins involved in cellular health), promoting autophagy (a form of cellular housekeeping), and increasing AMPK activity (an enzyme involved in metabolism regulation). Research indicates that fisetin elicits a similar response as calorie restriction, activating all three of these pathways as well. Furthermore, as we age, the activity of these pathways declines, but several studies in mice show that fisetin can increase their activity, helping to keep cells youthful.[5] 


Fisetin’s role as an antioxidant

Oxidative stress, another proposed theory for why we age, develops from an imbalance between free radicals and antioxidants in the body. Free radicals can damage cells, proteins, and DNA, while antioxidants help neutralize and minimize their harmful effects. As an antioxidant, fisetin helps to prevent the damage done by free radicals.[6] It also exerts anti-inflammatory properties by shutting off pathways that promote inflammation and decreasing the production of inflammatory compounds.[7]

Glutathione, often referred to as the “master antioxidant” in humans, works by protecting cells from damage and stress, particularly oxidative stress. Moreover, adequate glutathione levels may also help ward off many aging-related diseases, as low levels are linked to a higher incidence of diabetes, cancer, and heart disease. As we age, glutathione levels also tend to decline.[8] Research indicates that fisetin can help preserve the body’s supply of glutathione. For example, fisetin may influence two compounds, NrF2 and ATF4, that work to maintain glutathione levels. In a mouse model, when ATF4 and NrF2 were inhibited, fisetin’s ability to maintain glutathione dropped by up 30%.[9] 

Fisetin has a significant impact on health, especially in animal models. Clinical trials are currently underway to determine how this effectiveness will translate from animals to humans. Based on the best available evidence, our team of scientists at JUVICELL incorporated 250mg of high-quality fisetin into our supplement—a clinically safe and efficacious dose and the equivalent of eating 60 strawberries! JUVICELL also contains nine other clinically proven and effective longevity-enhancing ingredients, paving the way for the first-ever longevity supplement of its kind. Derived from nature and backed by science, JUVICELL can help to support longevity in healthy people.


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