Published by Paul Thompson |
Fact-checked against peer-reviewed sources | Updated March 2026
SENOLYTIC

# Fisetin: The Most Potent Natural Senolytic

Discover how this powerful flavonoid eliminates senescent "zombie" cells, reduces inflammation, and extends healthspan.

## What is Fisetin?

Fisetin is a naturally occurring flavonoid found in strawberries, apples, persimmons, onions, and cucumbers. While it has antioxidant properties, fisetin has gained attention primarily for its remarkable senolytic activity - the ability to selectively eliminate senescent cells.

Senescent cells, often called "zombie cells," are damaged cells that have stopped dividing but refuse to die. They accumulate with age and secrete inflammatory compounds (SASP) that damage surrounding healthy tissue, accelerating aging and disease.

In a landmark 2018 study at Mayo Clinic, fisetin was identified as the most potent natural senolytic compound tested, outperforming quercetin and other flavonoids in clearing senescent cells.

## How Fisetin Works

Fisetin eliminates senescent cells by targeting their survival pathways. Senescent cells rely on anti-apoptotic (anti-death) pathways to survive. Fisetin disrupts these pathways, particularly the BCL-2 family of proteins, triggering apoptosis specifically in damaged cells.

Importantly, fisetin is selective - it targets senescent cells while leaving healthy cells unharmed. This specificity makes it safer than non-selective approaches to clearing damaged cells.

### Fisetin's Key Actions

- Selectively eliminates senescent cells via BCL-2 pathway
- Reduces SASP inflammatory secretions
- Powerful antioxidant activity (10x more potent than quercetin)
- Crosses blood-brain barrier for neuroprotection
- Supports healthy immune function

## Mayo Clinic Research

The 2018 EBioMedicine study by researchers at Mayo Clinic tested fisetin in aged mice and found remarkable results. Fisetin reduced senescent cell markers in multiple tissues, extended median lifespan, and improved physical function even when given late in life.

The study showed that fisetin treatment reduced inflammation, improved tissue function, and extended healthspan - the period of life spent in good health. These benefits occurred even when treatment started in old age, suggesting it's never too late to benefit.

Human clinical trials are now underway, including studies on COVID-19 recovery and age-related frailty, to validate these promising animal findings in humans.

## Proof a Zombie Cell Is a Real Thing

Yes — senescent "zombie" cells are one of the most well-documented phenomena in modern cell biology, backed by over 60 years of peer-reviewed research published in the world's top scientific journals.

### Key Studies Proving Senescent Cells Are Real

- 1961 — Leonard Hayflick discovered cellular senescence at the Wistar Institute. He proved that normal human cells can only divide a finite number of times before entering permanent growth arrest. Published in Experimental Cell Research. This became known as the Hayflick Limit and is now textbook biology.
- 2008 — Judith Campisi (Buck Institute) discovered the SASP (Senescence-Associated Secretory Phenotype) — the toxic cocktail of inflammatory chemicals that senescent cells secrete into surrounding tissue. Published in Genes & Development. She was elected to the National Academy of Sciences for this work.
- 2011 — Baker, Kirkland & van Deursen (Mayo Clinic) published the landmark proof in Nature — the most prestigious science journal in the world. They engineered mice where senescent cells could be selectively killed. Clearing them delayed cataracts, muscle loss, and tissue dysfunction. Their conclusion: "cellular senescence is causally implicated in generating age-related phenotypes." (Nature, Vol 479, PMID 22048312)
- 2016 — Same Mayo Clinic team, also in Nature: clearing senescent cells from normally aging mice extended median lifespan by 25%. (Nature, Vol 530, Pages 184-189)
- 2019 — First human trial: James Kirkland at Mayo Clinic gave 9 patients dasatinib + quercetin for 3 days. Senescent cell markers were significantly reduced within 11 days. Published in EBioMedicine (The Lancet). (PMID 31542391)

There are currently 20+ active clinical trials testing senolytic drugs at Mayo Clinic and institutions worldwide. The NIH launched a $125 million SenNet program in 2022 specifically to map senescent cells in the human body.

Fisetin and quercetin are among the most promising natural compounds being studied to clear these cells. Read more about how they compare in our detailed guides:

- Quercetin vs Fisetin — Full Comparison
- Resveratrol vs Fisetin — Which Is Better for Anti-Aging?
- Best Anti-Aging Supplements 2026 — Ranked

## Senolytic Protocol

Unlike daily supplements, senolytics are typically taken intermittently in higher doses to maximize senescent cell clearance. This "hit and run" approach allows the body to clear the targeted cells and then recover.

The Mayo Clinic mouse studies used the equivalent of roughly 20mg/kg body weight. For a 70kg human, this translates to approximately 1,400mg. However, human optimal dosing is still being researched.

### Common Dosing Protocols

- Daily Antioxidant: 100-200mg per day continuously
- Monthly Senolytic: 500-1000mg daily for 2-3 consecutive days, once monthly
- Quarterly Protocol: 1000-1500mg daily for 2-3 days, every 3 months
- Best taken: With meals to improve absorption

## Fisetin + Quercetin Synergy

Fisetin and quercetin work through complementary mechanisms and are often combined for enhanced senolytic effect. Quercetin is more affordable and inhibits HSP90, while fisetin is more potent and targets BCL-2 pathways.

The combination may provide broader senolytic coverage than either compound alone. The "Fisetin + Quercetin" protocol has become popular in the longevity community, typically taken together during senolytic dosing periods.

Life Extension's Senolytic Activator combines both compounds along with black tea theaflavins for a comprehensive approach to senescent cell clearance.

## Safety and Considerations

Fisetin has been consumed safely in foods for centuries and is generally well-tolerated as a supplement. Clinical trials have not reported serious adverse effects at doses up to 1,400mg.

Potential interactions include blood thinners (fisetin may have mild anticoagulant effects) and certain medications metabolized by CYP enzymes. Consult a healthcare provider before starting high-dose senolytic protocols.

Some people report mild GI discomfort at higher doses. Taking with food typically resolves this issue.

## Top Fisetin Supplements

Premium senolytic formulas for clearing zombie cells and promoting longevity

BEST SELLER

### Double Wood Fisetin 100mg

Pure fisetin, third-party tested. 60 capsules for daily or intermittent use.

$19.95
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HIGH POTENCY

### ProHealth Pure Fisetin 250mg

High-potency formula for senolytic protocols. 60 capsules, maximum strength.

$55.95
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COMBO FORMULA

### Life Extension Senolytic Activator

Fisetin + Quercetin + Black Tea Theaflavins. Complete senolytic stack.

$18.00
View on Amazon