library.onepin.app/fisetin Peptide Education Library
Education only, not medical advice 21+ Every dose is an example to finalize with a licensed provider

OnePin Peptide Library · Longevity

Longevity Supplement Not FDA-approved · investigational Controlled substance

Fisetin

Senolytic Fisetin

SupplementFlavonoidSenolytic

Fisetin (3,3',4',7-tetrahydroxyflavone) is a naturally occurring flavonoid found in strawberries, apples, persimmons, onions, grapes, and cucumbers. It has emerged as one of the most potent senolytic compounds identified in preclinical research, meaning it can selectively eliminate senescent (aged, dysfunctional) cells that accumulate with aging and contribute to chronic inflammation, tissue dysfunction, and age-related diseases.,Research led by the Mayo Clinic (Kirkland, Tchkonia, and colleagues) and the Salk Institute (Maher and colleagues) has demonstrated that fisetin has senolytic activity superior to many other tested flavonoids in cell culture and animal models. In aged mice, fisetin treatment reduced senescent cell burden, decreased inflammatory markers, improved tissue function, and extended both median and maximum lifespan. These findings have generated significant interest in fisetin as an anti-aging intervention.,Fisetin is available as an over-the-counter dietary supplement. Human clinical trials are underway, including the AFFIRM trial at Mayo Clinic studying fisetin in elderly adults, and trials in COVID-19 patients and osteoarthritis. However, as of 2025, no large completed human trials have been published, and fisetin's senolytic efficacy in humans remains to be confirmed. Its oral bioavailability is notably poor due to rapid metabolism and low aqueous solubility, which is a significant challenge for clinical translation.

Quick Start
Route
Oral
Start low
500-2000mg
Frequency
Intermittent (2-3 consecutive days per month for senolytic protocol)
Timing
Take with a fat-containing meal to potentially improve absorption

Start here. Every protocol below is ordered lowest-first. Begin at the smallest effective dose, hold about a week to assess tolerance, and step up only if needed.

Tiered Protocols · lowest first
Quick Start
Conservative start
500-2000mg · Oral · Intermittent (2-3 consecutive days per month for senolytic protocol)
Lowest starting point. Hold about a week to assess tolerance before stepping up.
500-2000mg
Intermittent (2-3 consecutive days per month for senolytic protocol)
Standard
Mayo Clinic Senolytic Protocol
20 mg/kg · Oral · Daily
human clinical trial · Mayo Clinic AFFIRM Trial (NCT03430037)
20 mg/kg
Daily
01

How it works

Selectively induces apoptosis in senescent cells by inhibiting pro-survival pathways including PI3K/AKT/mTOR and BCL-2 family anti-apoptotic proteins (BCL-XL) that senescent cells depend on for survival, while sparing normal healthy cells.,Activates SIRT1 (sirtuin 1) and AMPK pathways involved in cellular stress response, autophagy, and metabolic regulation, contributing to anti-aging effects independent of senolytic activity.,Inhibits NF-kB signaling and reduces production of SASP (senescence-associated secretory phenotype) factors including IL-6, IL-8, TNF-alpha, and MMP-3, which are key drivers of age-related chronic inflammation and tissue damage.

Selectively induces apoptosis in senescent cells by inhibiting pro-survival pathways including PI3K/AKT/mTOR and BCL-2 family anti-apoptotic proteins (BCL-XL) that senescent cells depend on for survival, while sparing normal healthy cells.,Activates SIRT1 (sirtuin 1) and AMPK pathways involved in cellular stress response, autophagy, and metabolic regulation, contributing to anti-aging effects independent of senolytic activity.,Inhibits NF-kB signaling and reduces production of SASP (senescence-associated secretory phenotype) factors including IL-6, IL-8, TNF-alpha, and MMP-3, which are key drivers of age-related chronic inflammation and tissue damage.

02

What to expect

Early
Days 1–7

Days 1-7: Senescent cells begin undergoing apoptosis during and shortly after the dosing window. No dramatic subjective effects expected.

03

Evidence

HumanModerate
AnimalPresent
In-vitroPresent
2018Fisetin is a senotherapeutic that extends health and lifespan · Yousefzadeh MJ, Zhu Y, McGowan SJ, et al, EBioMedicine ↗peer reviewed
2009Modulation of multiple pathways involved in the maintenance of neuronal function during aging by fisetin · Maher P, Genes & Nutrition ↗review
2006Flavonoid fisetin promotes ERK-dependent long-term potentiation and enhances memory · Maher P, Akaishi T, Abe K, Proceedings of the National Academy of Sciences USA ↗peer reviewed
2017Fisetin Acts on Multiple Pathways to Reduce the Impact of Age and Disease on CNS Function · Maher P, Frontiers in Bioscience (Scholar Edition) ↗review
04

Interactions & stacking

What's safe to combine, and what belongs in a separate pin.

Safe & synergistic

NAD+NAD+ supports cellular repair pathways - may enhance recovery after senolytic cell clearance
MOTS-cMitochondrial peptide works through different pathways - no conflict with senolytic mechanism
MelatoninMelatonin's antioxidant properties complement fisetin's senolytic effects - no pharmacological conflict
Urolithin AMitophagy support and senolytic clearance are complementary aging interventions

Keep separate

Blood thinners (Warfarin)Flavonoids have mild antiplatelet activity - fisetin may potentiate anticoagulant effects
Chemotherapy agentsFisetin's senolytic activity may interfere with chemotherapy-induced senescence, which is sometimes a desired anti-tumor mechanism
05

Pharmacokinetics

Illustrative plasma concentration · 24 h
Half-life
~3-4 hours (parent compound). Rapidly metabolized to glucuronide and sulfate conjugates. Very low oral bioavailability (~1-5% in animal studies).
Peak · Tmax
~1-3 hours oral
Elimination
~15-20 hours
Activity
24-72 hours (senolytic apoptosis cascade continues after compound clearance)

Storage. Store in a cool, dry place away from light and moisture. Oral compound - no reconstitution needed. Some formulations recommend refrigeration for long-term storage.

06

Regulatory status

Dietary supplement (OTC) in the United States. Not FDA-approved for any medical indication. GRAS as a food component. Multiple clinical trials registered at ClinicalTrials.gov (including AFFIRM at Mayo Clinic). Not a controlled substance.

Put it to work

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Open Fisetin straight into OnePin with your vial and dose pre-filled, then let it handle the syringe math and remind you before the vial runs out.

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Go deeper

The guide & community

The complete Fisetin walkthrough, real protocol discussion and coaching live inside the BlessUp community on Skool.

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