Fisetin for clearing out senescent cells

Is it worth trying?

Fisetin is a flavonoid found at low levels in fruits and vegetables, such as strawberries, persimmons, and onions. We get about 0.4mg/day from our diet, but it is also available as a supplement at much higher doses.[ref]

Studies over the past few years show that fisetin acts as a senolytic, clearing out senescent (zombie) cells. Senolytics are compounds that selectively eliminate senescent cells, and fisetin was found to be one of the most potent plant-based senolytics in animal studies.

Senescent cells are ones that have reached the end of their lifecycle and need to be cleared out by the immune system. Senescent cells stop dividing but remain metabolically active, secreting pro-inflammatory cytokines. This happens all the time, and in young people, the immune system naturally takes care of senescent cells.

As we age, the rate of cellular senescence outstrips the immune system’s ability to clear the cells out. This is a problem because senescent cells give off inflammatory signals, which cause inflammation and problems for surrounding cells. The chronic accumulation of senescent cells contributes to chronic inflammation, an underlying cause of most age-related diseases

Excess senescent cells are thought to drive aging by two pathways:

• Stem cells becoming senescent can lead to a decreased ability for stem cells to renew tissue.

• An increased number of senescent cells can cause chronic inflammation.[ref]

Senolytics are drugs that can clear out senescent cells. Initial studies on senolytics used chemotherapy drugs, such as dasatinib. Researchers found that dasatinib plus quercetin cleared out senescent cells and increased healthspan in animals.[ref][ref] Natural senolytics are of interest because they potentially will have fewer side effects - and wider accessibility - than chemo drugs.

Here’s a screenshot from an overview article on fisetin as a senolytic to give you an idea of what is going on with increased senescence in aging.

Let’s dig into the research of what is currently known about fisetin as a senolytic.

Fisetin as a natural senolytic:

In 2018, researchers screened a panel of flavonoids and found that fisetin acts as a senolytic and was the most effective out of the 10 plant flavonoids tested. They showed that fisetin extends healthspan and lifespan by about 10% in mice. The researchers were ablet to clear out 25-50% of senescent cells with high-dose fisetin for a few days.[ref]

Since then, a bunch of studies on fisetin have been conducted:

• At lower doses, fisetin increases glutathione, acting as an antioxidant. [ref]

• Fisetin also reduces the formation of methylglyoxal, which is what forms advanced glycation end products (AGEs). [ref]

• In cell studies, fisetin inhibits mast cells from releasing inflammatory cytokines (IL-31, IL1B, IL4, IL6, TNF-alpha, and NF-κB) and inhibits histamine release.[ref][ref][ref]

• In cell studies using fat cells, fisetin “works in a dose-dependent manner and selectively attenuates these markers of senescence”.[ref]

As a senolytic:

Animal studies show great results for fisetin as a senolytic.

• A new study (April 2025) showed that fisetin cleared out senescent cells in animals with diabetes. This improved cardiovascular function significantly.[ref]

• A 2024 study in mice showed that intermittent dosing of fisetin improved endothelial function significantly.[ref]

• In mice and human skin cells, fisetin eliminates senescent skin cells.[ref]

There are a number of clinical trials underway that are investigating fisetin as a senolytic to reduce markers of aging. Most of the human trials are in early phases and with limited results so far. Essentially, they use a large dose of fisetin for a cycle of a couple of days every few months. The theory is that this helps to kill senescent cells, and then gives the body time to clear everything out. Cellular senescence is necessary, at the right level, for things like wound healing, so you don’t want to decrease it continually.

Here are some of the clinical trials that are ongoing or have results:

• The Mayo Clinic has several clinical trials using 20 mg/kg/day for 3 days per month. For someone who weighs 100kg (220 lbs), this would equate to around 4g/day. Similarly, for someone who weighs 50kg (110 lbs), this would be 2g/day. The study used high doses for three days per month for five months.

• One of the phase II Mayo Clinic clinical trials that looked at both fisetin and dasatinib plus quercetin showed that there was no improvement in bone health in postmenopausal women.[ref] The other clinical trials haven’t posted results yet.

• A clinical trial in Egypt is using 1250 mg/day quercetin + 1000mg/day Fisetin for 3 consecutive days every 3 weeks with a primary endpoint of the effect on knee pain. No results have been posted yet on this trial either.

• A larger phase II clinical trial with 220 elderly patients is testing fisetin at 20mg/kg/day for two days in patients with sepsis. The reasoning here is that senescent immune cells increase with age and are a potential contributor to sepsis.[ref]

• A small study comparing dasatinib, quercetin, and fisetin using DNA methylation clocks showed that dasatinib plus quercetin increased biological age using one ‘clock’ but had positive effects when using other methylation tests. Adding in fisetin made the aging slightly worse.[ref] (I’m honestly not sure what to think of this study, and I don’t really think DNA methylation age clocks are all that accurate. Here’s my article on epigenetic age clocks — including the study on how the time of day of testing makes up to a 5-year difference in the biological age results!)

My takeaway:
Studies show clear benefits in specific types of tissue - e.g. the studies on endothelial function or adipose tissue - but the human clinical trial didn’t show a positive benefit for bone health or for beating the epigenetic age clock tests. Cellular senescence may be different or need a different senolytic depending on the tissue or organ system. More research is needed…

Cautions with fisetin:

If you’re taking any type of prescription medication, be sure to talk to your doctor and your pharmacist before taking fisetin, especially at higher doses. Fisetin seems to be safe in animal and early phases of human clinical trials, but long-term studies are needed to know if it is safe to take for years instead of just months.

For example, studies on fisetin for neuroprotection in stroke patients show that it effectively delays clotting time and preserves mitochondrial function, which is good, but this likely means that caution should be used in taking fisetin for anyone on anticoagulants.[ref]

For people with slow COMT function (check here), please know that fisetin further inhibits COMT. This also could interact with medications that are metabolized by COMT.

If you have any questions at all on whether fisetin could be a problem for you, talk with your doctor. There are questions around kidney issues.

Types of fisetin supplements:

Bio-fisetin from LifeExtension uses a complex with galactomannans from Fenugreek seeds to increase bioavailability. Studies on it show that the encapsulation of fisetin in the fenugreek galactomannan hydrogel increased absorption and serum levels by 26-fold. [ref]

High dose options: Many fisetin supplements contain 100 mg, which may be effective for reducing inflammation, but to use them as a senolytic, you may end up taking 10 capsules. The other option here is to get powdered fisetin, such as from Bulk Supplements. Fisetin is more bioavailable with fat, so taking it with a source of fat (e.g. yogurt) may be helpful. There are also liposomal options (none from brands that I’m familiar with, though).

Fisetin is still somewhat new as a supplement, and there seem to be quite a few studies on different ways to encapsulate it or use nano-formulations.

Conclusion:

The studies in animals and cell lines are impressive for senolytics, but human trials take a while and often have ambiguous results.

My guess is that specific senolytics will target some specific tissues more effectively than others. Becoming more resilient to aging and targeting a long healthspan will likely take a multi-pronged approach. Senolytics are likely to be part of the approach, but it may be that multiple senolytics will be needed.