Longevity & Mitochondrial Research Preliminary

Fisetin

Flavonoid polyphenol (found in strawberries, apples) studied as a senolytic — selectively clears senescent "zombie" cells. Mayo Clinic clinical trials ongoing for frailty and age-related conditions.

senolyticsenescenceflavonoidlongevityinflammationagingzombie cells
Half-life
2–4 hours; rapid metabolism; intermittent high-dose "burst" protocols common in research
SKUs
1
Evidence
Preliminary

Fisetin is a naturally occurring flavonoid found in strawberries, apples, persimmons, and other fruits and vegetables. It has generated significant research interest as a potential senolytic agent — a compound that selectively clears aging cells (senescent cells) from the body. It is also studied for anti-inflammatory and neuroprotective properties. Human trials are underway but early-stage.

Senolytic Research
Fisetin is among the compounds studied by aging researchers for its ability to selectively trigger cell death in senescent cells — cells that have stopped dividing, resist dying, and secrete inflammatory signals. Animal studies from the Mayo Clinic and other institutions showed that fisetin eliminated senescent cells and extended healthspan in aged mice.
Neuroprotective Research
Cell and animal studies have examined fisetin for protection against neurodegeneration. It has shown effects on memory and learning in animal models of Alzheimer's disease and normal aging, reducing amyloid pathology and inflammation in some studies.
Anti-Inflammatory Research
As a flavonoid, fisetin inhibits multiple inflammatory pathways including NF-kB and reduces production of inflammatory cytokines. These effects have been documented in cell culture and animal studies.
Human Trials
Early-phase human trials (including from the Mayo Clinic's SToMP-AD trial) have been conducted to evaluate safety and feasibility of fisetin dosing in older adults and Alzheimer's patients. These trials focus on safety and biomarker changes rather than clinical outcomes.
  • Animal studies show senescent cell clearance and healthspan extension in aged mice.
  • Neuroprotective effects and improved cognitive performance in multiple rodent Alzheimer's models.
  • Anti-inflammatory effects documented in cell culture and animal research.
  • Early human trials confirm it is well-tolerated at studied doses.
  • Clinical efficacy in humans has not yet been demonstrated in completed trials.

Fisetin has notable bioavailability challenges — it is rapidly metabolized and has inconsistent absorption, making it difficult to achieve the concentrations in human tissue that produce effects in cell and animal studies. Human efficacy data do not yet exist in completed trials. The senolytic effects seen in animals have not been confirmed in humans. It is widely available as a supplement, but supplement-grade products may vary significantly in quality and actual fisetin content.

As cells age, some of them enter a state called senescence — they stop dividing normally but refuse to die. These zombie-like cells sit in tissues producing inflammatory signals that gradually damage surrounding healthy cells. Researchers believe the accumulation of senescent cells is a significant driver of aging-related decline. Fisetin appears to selectively activate programmed cell death pathways in these senescent cells while largely leaving healthy cells alone — a property called senolytic activity. It also acts as an antioxidant and reduces inflammatory signaling more broadly. In animal studies, periodic high-dose fisetin treatment appears to reduce the senescent cell burden and improve various markers of aging.

Fisetin is generally considered safe in human studies conducted to date, with no significant adverse effects reported at doses up to 20mg/kg in early trials. It is available as an over-the-counter supplement. Oral bioavailability is low and variable. There are no known serious drug interactions, though it may interact with medications that are substrates of certain liver enzymes. It is not FDA-approved as a drug for any indication.

Preliminary

Most evidence comes from preclinical studies and case reports. Human data is limited and more research is needed.

Published Research Ranges
20mg/kg intermittent (burst dosing) per Mayo protocol extrapolations; human trials 100–1000mg/day being evaluated
Research Context Only: These are ranges reported in published scientific studies for educational reference. They are not dosing recommendations. This is not medical advice. Always consult a qualified healthcare professional.

Sources listed here are from the platform research library. All links open the original publication. No citations are generated by AI.

Fisetin Is a Senotherapeutic That Extends Health and Lifespan
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Fisetin as a Caloric Restriction Mimetic Improves Healthspan in Aging Mice
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Neuroprotective Effects of Fisetin: SIRT1-Dependent Mechanisms
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Senolytic Therapy to Modulate the Progression of Alzheimer's Disease (SToMP-AD): A Pilot Clinical Trial
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Cellular Senescence: Molecular Targets, Biomarkers, and Senolytic Drugs
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Why Senescent Cells Are Resistant to Apoptosis: An Insight for Senolytic Development
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Senescence and cancer - role and therapeutic opportunities
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Flavonoids as Potential Anti-Inflammatory Molecules: A Review
 • 2022  • DOI: 10.3390/molecules27092901
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Therapeutic application of quercetin in aging-related diseases: SIRT1 as a potential mechanism
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Mechanisms and therapeutic implications of cellular senescence in osteoarthritis
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Strategies for Targeting Senescent Cells in Human Disease
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Senolytic Drugs: Reducing Senescent Cell Viability to Extend Health Span
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Cellular Senescence in Brain Aging
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Skin Aging, Cellular Senescence and Natural Polyphenols
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Natural Compounds for Alzheimer's Disease Therapy: A Systematic Review of Preclinical and Clinical Studies
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Flavonoids as Therapeutic Agents in Alzheimer's and Parkinson's Diseases: A Systematic Review of Preclinical Evidences
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Homeostasis and metabolism of iron and other metal ions in neurodegenerative diseases
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Cellular senescence and SASP in tumor progression and therapeutic opportunities
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Oxidative Stress: The Role of Antioxidant Phytochemicals in the Prevention and Treatment of Diseases
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Polyphenols Targeting NF-κB Pathway in Neurological Disorders: What We Know So Far?
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The role of CXCL family members in different diseases
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Neuroprotective Potentials of Flavonoids: Experimental Studies and Mechanisms of Action
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Prostate Cancer Review: Genetics, Diagnosis, Treatment Options, and Alternative Approaches
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Natural Products as Anticancer Agents: Current Status and Future Perspectives
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Nrf2 Regulates Oxidative Stress and Its Role in Cerebral Ischemic Stroke
 • 2022  • DOI: 10.3390/antiox11122377
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Plant Secondary Metabolites Produced in Response to Abiotic Stresses Has Potential Application in Pharmaceutical Product Development
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Interplay between PI3K/AKT pathway and heart disorders
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Impairment of the autophagy-lysosomal pathway in Alzheimer's diseases: Pathogenic mechanisms and therapeutic potential
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The Interaction of Polyphenols and the Gut Microbiota in Neurodegenerative Diseases
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Skeletal Aging and Osteoporosis: Mechanisms and Therapeutics
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Dietary Flavonoids: Cardioprotective Potential with Antioxidant Effects and Their Pharmacokinetic, Toxicological and Therapeutic Concerns
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Black Cumin (Nigella sativa L.): A Comprehensive Review on Phytochemistry, Health Benefits, Molecular Pharmacology, and Safety
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Tau Oligomers Neurotoxicity
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Anti-Oxidative, Anti-Inflammatory and Anti-Apoptotic Effects of Flavonols: Targeting Nrf2, NF-κB and p53 Pathways in Neurodegeneration
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The role of cellular senescence in ageing and endocrine disease
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Therapy-Induced Senescence: An "Old" Friend Becomes the Enemy
 • 2020  • DOI: 10.3390/cancers12040822
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Reducing Senescent Cell Burden in Aging and Disease
 • 2020  • DOI: 10.1016/j.molmed.2020.03.005
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Senescent Cells: Emerging Targets for Human Aging and Age-Related Diseases
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Important Flavonoids and Their Role as a Therapeutic Agent
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Flavonoids as Anticancer Agents
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RNA packaging into extracellular vesicles: An orchestra of RNA-binding proteins?
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59 sources · Platform research library · Not generated by AI

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Research Education Only: This profile is for educational purposes only. All information is sourced from published scientific literature. This is not medical advice. Not for human consumption. Consult qualified medical professionals for any health decisions.