Rankings / Longevity — Senolytics & Polyphenols

Fisetin

Longevity · Senolytic / polyphenol

Tier B-

Reviewed by Read Off Label · Last reviewed · How we grade

mtor-inhibitionsenolyticpolyphenolantioxidantanti-inflammatoryotc
6.2 / 10
Tier B-
Ev 4 Bn 5 Sf 9

Bottom line

Read Off Label grades Fisetin as B- (6.2/10) based on preclinical-moderate evidence, variable benefit magnitude, and a low-risk safety profile.

Yousefzadeh 2018 demonstrated senolytic activity in naturally aged mice.

Studied, labeled, or reported-use context: 20 mg/kg for 2 consecutive days monthly ("hit and run"); or daily low-dose — OTC; not individualized guidance.

Frontier potential — editorial judgment, not evidence

This is a separate axis from the grade above. It asks a different question: if this worked in humans, how much would it matter? It is our judgment, it is not part of the composite score, and it cannot raise a grade. A high number here is a statement about the idea, not about whether it works or whether anyone should take it.

5/10
Real mechanism, modest ceiling Phase 2

What the ceiling rests on

The senolytic with the best safety margin — a flavonoid found in food, with mouse work showing senescent-cell clearance and extended median and maximum lifespan even when started late in life. Currently in Mayo Clinic clinical trials, which is further than most senolytic candidates.

Why it may not get there

Oral bioavailability is poor and the doses used in mouse work are far above anything achieved by ordinary supplementation. Human trial results have not read out. The "hit and run" monthly protocol circulating in the community is extrapolated from animal dosing, not established in people.

What would change this Readout of the Mayo Clinic senolytic trials.

What the evidence says

Yousefzadeh 2018 demonstrated senolytic activity in naturally aged mice. Mayo Clinic AFFIRM-LITE and AFFIRM trials in frailty and COVID. Safer profile than dasatinib; used in DIY senolytic protocols despite absent clinical outcome evidence.

Mechanism

Flavonol; more potent senolytic than quercetin in preclinical assays; also inhibits mTOR; PI3K/AKT modulation; anti-inflammatory and antioxidant

Studied, labeled, or reported dose & route

20 mg/kg for 2 consecutive days monthly ("hit and run"); or daily low-dose

This records doses and routes described in studies, approved labeling, clinical practice, or documented use. It is not individualized guidance and does not establish safety; context changes with indication, formulation, health history, monitoring, and other medicines.

Citations

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Common questions

What does the evidence show about Fisetin's effects?
Read Off Label rates the evidence for Fisetin as Preclinical-Moderate and the benefit magnitude as variable, producing an overall grade of B- (6.2/10). Yousefzadeh 2018 demonstrated senolytic activity in naturally aged mice.
What safety findings are reported for Fisetin?
Fisetin has a low risk profile in the database. Low Legal status: OTC.
What doses or routes are reported for Fisetin?
20 mg/kg for 2 consecutive days monthly ("hit and run"); or daily low-dose This is context from studies, approved labeling, clinical practice, or documented use; it is not individualized guidance and does not establish safety.
How does Fisetin work?
Flavonol; more potent senolytic than quercetin in preclinical assays; also inhibits mTOR; PI3K/AKT modulation; anti-inflammatory and antioxidant

This is an independent synthesis of published research by a non-clinician. Scores are opinions supported by citations, not prescriptions. See the full disclaimer and methodology for how this score was produced and what it does and doesn't mean.