Longevity Articles

Fisetin Supplementation: A Promising Approach to Combating Brain Aging

Fisetin Supplementation: A Promising Approach to Combating Brain Aging

Anti-aging and longevity are topics of increasing interest as the global population continues to age. While genetics play a large role in determining our lifespan, lifestyle choices such as diet and exercise also play a significant role in how we age. One area that has gained attention in recent years is the use of supplements to support anti-aging and longevity. There are numerous supplements that have been studied for their anti-aging potential, ranging from vitamins and minerals to antioxidants, herbs and botanicals and amino acids.

In this article, we will explore fisetin, a naturally occurring antioxidant known for its anti-aging and longevity benefits. We will also explore how you can increase your fisetin intake through supplementation.

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What is Fisetin?

Fisetin is a flavonoid, which is a type of natural compound found in fruits such as strawberries, apples, and persimmons, as well as in vegetables such as onions and cucumbers. Fisetin has been studied for its potential health benefits, including its antioxidant and anti-inflammatory properties. Some research suggests that fisetin may have the ability to protect cells from damage caused by free radicals. Additionally, some experts found that fisetin might help to protect the brain and improve memory and cognitive function.

Fisetin was first isolated from the Venetian sumach plant (Rhus cotinus) in 1833 and was studied extensively for its structure around the 1890s. The Venetian sumach is a small tree or shrub that is native to the Mediterranean region and parts of Asia and is also known by the names "dyer’s sumach" or "European smoketree." The plant has been traditionally used in the Mediterranean region as a dye and ornamental plant. The isolation of fisetin from the Venetian sumach was one of the earliest examples of the isolation of a flavonoid.

Flavonoids are a diverse group of naturally occurring compounds that are widely distributed in the plant kingdom. They play a variety of important roles in plants, including providing coloration, protecting against UV radiation and disease-causing pathogens, and serving as signaling molecules. All these mechanisms help to keep the plant healthy and promote survival and reproduction.

Health Benefits of Fisetin

Fisetin is equally beneficial to human bodies as it is to plants. Studies suggest that fisetin may have a variety of potential health benefits for humans, including:

1. Antioxidant Properties

Fisetin has been shown to have senolytic properties, which means that it can help eliminate senescent cells. Senescent cells are cells that have stopped dividing and can no longer perform their normal functions but are not yet dead. These cells can accumulate with age.

Fisetin's antioxidant properties play a key role in its senolytic effects. Antioxidants are substances that can protect cells from damage caused by free radicals, which are highly reactive molecules that can damage cells by reacting with important cellular components such as DNA, proteins and lipids. This damage is known as oxidative stress, and over time, it can accumulate and trigger the senescence process.

Fisetin can "hunt down" free radicals and prevent them from causing damage to cells. This can help to protect cells from becoming senescent and can also trigger a natural process called apoptosis, which is the self-destruction of damaged or unwanted cells, including senescent cells.

Additionally, fisetin has been shown to target specific pathways known to be involved in the senescence process, such as the PTEN-PCKδ signaling pathway, which slows down the aging process. It has also been shown to increase the activity of the body’s natural antioxidants, which are similarly capable of neutralizing free radicals and protecting cellular parts from damage. 

2. Anti-inflammatory Properties

Inflammation is a natural response of the body's immune system to injury or infection. It is characterized by the release of chemical mediators called cytokines, which cause inflammation and the recruitment of immune cells to the site of injury or infection. While acute inflammation is a beneficial reaction that helps to heal injuries and fight off infections, chronic inflammation isn’t as helpful and can actually do more damage.

Fisetin works by diminishing the levels of certain chemicals in the body called proinflammatory cytokines, which are responsible for causing inflammation. Fisetin has been shown in studies to reduce the production of these chemicals, such as TNF and IL-6, which aids in the reduction of inflammation in the body.

Fisetin also works by inhibiting the activation of certain cells in the immune system called macrophages and neutrophils, which also play a key role in the inflammatory response. This can help reduce the infiltration of immune cells into your body’s tissues and decrease inflammation as well.

3. Brain and Cognitive Function

Your brain is particularly vulnerable to oxidative stress and inflammation, and fisetin, owing to its antioxidant and anti-inflammatory properties, can help to protect the brain from damage and improve memory and cognitive function.

Studies have found that fisetin can improve memory in animal models of age-related memory impairment. It has been shown to increase the expression of brain-derived neurotrophic factor (BDNF), which is a protein that promotes the growth and survival of nerve cells in the brain. BDNF is important for memory and learning, and its levels decrease with age, contributing to cognitive decline. Fisetin has been shown to have the potential to improve cognitive performance, including working memory and spatial memory, through several mechanisms.

BDNF is important for the formation and plasticity of synapses, which are the connections between nerve cells that are critical for cognitive function. Studies have concluded that fisetin can thus improve working memory in animals through the action of BDNF. Working memory pertains to your ability to hold information in your mind for a short period of time and manipulate it to complete a task.

Spatial memory, on the other hand, is your ability to remember the location of objects and navigate your space. Research demonstrates that fisetin can improve spatial memory in animals by increasing the number of new neurons in the hippocampus, a brain region that is critical for spatial memory. Additionally, fisetin has been shown to have the potential to boost the number of dendrites, which are branches of nerve cells that receive signals from other neurons, and improve synaptic plasticity, which allows the brain to adapt in response to new information.

It is worth noting that most of the studies on fisetin's cognitive benefits have been conducted in animal models, and more research is needed to confirm its effects in humans. However, these studies suggest that fisetin is promising as a dietary supplement for improving cognitive performance.

Increased Fisetin Intake Through Supplementation

We have talked about how fisetin can be found in a wide variety of natural sources. However, because the concentration of fisetin in fruits and vegetables comes in trace amounts, supplementation can help you fully take advantage of everything this flavonoid has to offer.

Fisetin Pro Longevity capsules provide a convenient and accessible way of increasing your fisetin levels. Apart from delivering all the health effects of fisetin, it also boasts of a proprietary Lifespan Absorption Blend™ responsible for improving the supplement's bioavailability, which pertains to the amount of fisetin that enters your body and produces an active effect. If you believe that you may benefit from fisetin supplementation, connect with our Nutrition Advisor, Joe Condora, through our free nutrition consultation program. 



Cordaro M, D'Amico R, Fusco R, et al. Discovering the Effects of Fisetin on NF-κB/NLRP-3/NRF-2 Molecular Pathways in a Mouse Model of Vascular Dementia Induced by Repeated Bilateral Carotid Occlusion. Biomedicines. 2022;10(6):1448.

Grynkiewicz G, Demchuk OM. New Perspectives for Fisetin. Front Chem. 2019;7:697.

Jacob S, Sumathi T. Extenuation of in utero toxic effects of MeHg in the developing neurons by Fisetin via modulating the expression of synaptic transmission and plasticity regulators in hippocampus of the rat offspring. Chem Biol Interact. 2019;305:3-10.

Jiang K, Yang J, Xue G, Dai A, Wu H. Fisetin Ameliorates the Inflammation and Oxidative Stress in Lipopolysaccharide-Induced Endometritis. J Inflamm Res. 2021;14:2963-2978.

Kashyap D, Garg VK, Tuli HS, et al. Fisetin and Quercetin: Promising Flavonoids with Chemopreventive Potential. Biomolecules. 2019;9(5):174.

Kim SG, Sung JY, Kang YJ, Choi HC. Fisetin alleviates cellular senescence through PTEN mediated inhibition of PKCδ-NOX1 pathway in vascular smooth muscle cells [published online ahead of print, 2023 Jan 11]. Arch Gerontol Geriatr. 2023;108:104927.

Li W, Qin L, Feng R, et al. Emerging senolytic agents derived from natural products. Mech Ageing Dev. 2019;181:1-6.

Liu SH, Lin CH, Hung SK, Chou JH, Chi CW, Fu SL. Fisetin inhibits lipopolysaccharide-induced macrophage activation and dendritic cell maturation. J Agric Food Chem. 2010;58(20):10831-10839.

Lorthongpanich N, Mahalapbutr P, Rungrotmongkol T, Charoenwongpaiboon T, Prousoontorn MH. Fisetin glycosides synthesized by cyclodextrin glycosyltransferase from Paenibacillus sp. RB01: characterization, molecular docking, and antioxidant activity. PeerJ. 2022;10:e13467.

Yousefzadeh MJ, Zhu Y, McGowan SJ, et al. Fisetin is a senotherapeutic that extends health and lifespan. EBioMedicine. 2018;36:18-28.

Zhan JQ, Chen CN, Wu SX, et al. Flavonoid fisetin reverses impaired hippocampal synaptic plasticity and cognitive function by regulating the function of AMPARs in a male rat model of schizophrenia. J Neurochem. 2021;158(2):413-428.

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