Can fisetin help reverse aging?

Fisetin is becoming more popular as another potential source of the scientific fountain of youth. It is a class of drugs that may help in giving you a longer lifespan, better health and an improved body. But how true is it that fisetin can reverse aging in humans?

Fisetin is basically a senolytic that has been used for clinical trials and studies on mice. These rigorous research studies have come up with the conclusion that fisetin may indeed reverse aging by killing senescent cells. However, you need to consume an extremely large amount of fisetin for it to work. Before we further understand how it potentially reverses the natural process of aging, let’s first identify fisetin. 

What is fisetin?

Fisetin is a plant polyphenol and a bioactive flavonoid–a wide category of compounds that mainly helps plants by providing vibrant hues and supporting health with antioxidant activity. 

There are several types of fisetin that you can find, and one of these is the traditional yellow or ochre dye that is commonly called fustic. This fisetin type is extracted from the wood of the smoke bush and used to colour fabrics and clothes until synthetic dyes eventually replace it.

These are bioactive compounds that occur naturally in plant-based foods, from fruits to even wine and chocolate
Photograph: Microgen/Shutterstock

Moreover, fisetin can be found in many trees and plants, such as Acacia Greggii, Butea Frondosa, Eudicotyledons, Quebracho Colorado and Rhus Cotinus. Despite its recent fast emergence in the market, it was actually first used in 1833 that was taken from the smoke bush of Rhus Continus. Today, fisetin is introduced as the main component of certain dietary supplements [1]. 

Additionally, this bioactive flavonol functions in your body by scavenging free radicals and fighting oxidative stress, which refers to the buildup of inflammatory and reactive compounds that damage cells and DNA. If not prevented, oxidative stress can lead to fatal diseases. 

Fisetin can be found in fruits and vegetables, primarily in apples, grapes, persimmon, strawberries, onions and cucumber. Among these mentioned rich sources of fisetin, strawberry has the highest amount of fisetin. 

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How can fisetin reverse aging?

To put it simply, fisetin prevents you from aging by reducing your body’s inflammation, which can cause chronic illnesses and aging. It further extends its anti-aging capabilities by aiding in preventing oxidative damage in your body that can lead to accelerated aging and degenerative diseases. With fisetin’s function that mimics the effects of a calorie-restricted diet, it can also help boost your immune system and increase your longevity. 

Experts suggest that the plant extract fisetin can help increase lifespan by 10 percent. Fisetin works on reversing aging by inhibiting specific cellular pathways that affect the factors of aging. A group of researchers has studied the effect of fisetin in rodents, particularly on aging and longevity. They concluded that the mice which were exposed to fisetin surprisingly lived 10 percent longer and had fewer age-related problems. 

Fisetin activates sirtuins

Fisetin works as an antiaging agent by activating your body’s sirtuins. Sirtuins refer to a family of signaling proteins that contributes to your metabolic regulation. They are cellular protectors that can be found in all cells of your body and are essential components of cells to keep them performing at peak levels. 

As you age, your sirtuin functions decline, and this is where fisetin steps in. Fisetin can activate your sirtuin function in cells to counter the decline. With this function of fisetin, you may extend your lifespan [2]. 

Fisetin acts as a senolytic to extend lifespan

Fisetin can extend lifespan as a result of different experiments. It shows that it can extend life by 50 percent when experimented with in yeast and 23 percent in flies. Additionally, some research suggests that fisetin can lengthen health span by decreasing the risk of developing several age-related diseases. 

Another way that fisetin reverses aging is by functioning as a potent senolytic. Fisetin is known as one of the few that can naturally provide senolytic agents, particularly during experiments in animals. Aside from reducing the number of senescent cells–cells that contribute to the body’s aging and age-related diseases–it also helps in extending lifespan. Fisetin is involved in inhibiting mTOR pathway, restoring tissue homeostasis and decreasing aging-related pathology [3]. 

Moreover, experts believe that cell senescence can directly contribute to aging. These senescent cells in your body are old cells with damaged DNA that have lost their ability to divide–this is why it is also called zombie cells. Senescent cells do not die, but they accumulate and inflame cells and tissues around them. When this happens, senescent cells can weaken your body and make it more susceptible to age-related diseases. 

To eradicate and counter senescent cells, your body needs senolytics, which are compounds helping your body to fight off the bad functions of senescent cells, specifically age-related diseases. Senolytics can even mitigate those that may have already developed and inflamed. Additionally, fisetin is a powerful senolytic among other kinds of flavonoids. 

In fact, a study suggests that fisetin can significantly eradicate senescent cells when applied to human umbilical vein endothelial cells. It is also the most effective compared with other plant-derived senolytics in destroying senescent cells in animals and humans [4]. 

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Fisetin’s role as antioxidant 

Oxidative stress is another contributor to your body’s natural aging process. You may have oxidative stress when there is an imbalance between your body’s free radicals and antioxidants. Generally, free radicals can put your healthy cells, proteins and DNA at risk of damage, whilst antioxidants help in neutralising and minimising harmful effects. 

With fisetin’s composition, it can serve as an antioxidant that protects your cells from free radical damage and exhibits anti-inflammatory properties by turning off pathways that promote inflammation and decreasing the production of inflammatory compounds.

Fisetin mimics calorie restriction 

The calorie restriction generally follows the rule to reduce your everyday calorie intake by 10 to 40 percent, and it is scientifically proven and effective in improving health and longevity. Fisetin promotes autophagy, which is a form of cellular housekeeping and increases AMPK, which is an enzyme involved in cellular metabolism activity. Fisetin is found to elicit the same effects as calorie restriction in your body. Also, the experiments in mice showed that fisetin could keep cells youthful. 

With fisetin’s functions of activating sirtuins, eradicating senescent cells, serving as an antioxidant and providing a calorie restriction effect in our body, fisetin is a great contender in reversing aging. 

Foods that are rich in fisetin

Fisetin can be consumed through supplements available in the market and natural processes like eating foods that are rich in fisetin. Like any other flavonoids, you can get fisetin in fruits and vegetables. 

Strawberries are at the top of the list as they have over 160 grams of fisetin. Next are apples with 27 grams and persimmons with 11 grams. Fisetin can also be found in onions with 5 grams, while grapes have 4 grams and kiwi with 2 grams. 

one of several types of flavonoids found in plants and plant-based foods

Some other sources of this dietary flavonoid are mangoes, tomatoes, cucumbers, nuts and wine that has shown strong anti-inflammatory, anti-oxidant, anti-tumorigenic, anti-invasive, anti-angiogenic, anti-diabetic, neuroprotective and cardioprotective effects in cell culture and in animal models relevant to human diseases.

Since fisetin only occurs in plants that are low concentrations, many people opt to take fisetin supplements instead. For fisetin dietary supplements, you can typically find brands that emphasise cellular health, antioxidants and healthy aging as their main functions. 

Surprisingly, all clinical studies about fisetin conducted in animals have not yet determined the recommended dosage of taking fisetin, as clinical trials in humans are not yet fully established. However, generally, the average daily intake of fisetin from food sources can be estimated to be only 0.4 mg, but most supplements contain much more than this [5]. 

The majority of fisetin supplements suggest taking around 100 to 500 mg per day–this includes the clinical trial with cancer patients that used 100 mg per day. In an ongoing clinical trial on older adults about fisetin’s effects on them, the researchers used a higher dose of 200 mg per kilogram of the participant’s body weight for two consecutive days. The participants with 155 pounds have taken 1,400 mg per day; however, this dose is not recommended. 

Moreover, you can safely take smaller doses of around 100 to 500 mg of fisetin per day, while higher doses of fisetin, typically about 1000 mg or more, are recommended to be taken at least a couple of days in a month. However, more clinical data and studies in humans are needed conduct before we can settle with a much more comprehensive recommended dose and timing of taking fisetin. 

If you are thinking of why not just eat a lot of strawberries since it has a good number of grams of fisetin, you can, but fisetin is generally poorly absorbed by the body. Studies have shown that taking fisetin with fats may increase its bioavailability. This is why many supplement manufacturers need to add certain oils to their supplement formulations. Hence, many people still choose to take fisetin supplements. 

The bottom line: 

Fisetin can be a top contender in reversing aging and lengthening lifespan. Although there are still some significant questions that require clinical studies, what we presently have can give us a ground-breaking possibility of longevity.

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[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3689181/ 
[2] https://www.lifeextension.com/magazine/2020/ss/fisetin-a-senolytic-for-longevity 
[3] https://pubmed.ncbi.nlm.nih.gov/30279143/ 
[4] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5391241/ 
[5] https://thenutritioninsider.com/wellness/fisetin-benefits/ 

Photograph: Sergii Gnatiuk/Shutterstock
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