Dasatinib + Quercetin (Senolytic Stack) vs Fisetin

Mechanism

Dasatinib is a multi-kinase inhibitor (targeting SRC, ABL, c-KIT, PDGFR, and ephrin receptors) originally developed for chronic myeloid leukemia. Quercetin is a natural flavonoid that inhibits PI3K, serpine/PAI-2, BCL-xL, and other anti-apoptotic pathways. Together, they constitute a senolytic combination that selectively induces apoptosis in senescent cells by disabling the senescent cell anti-apoptotic pathways (SCAPs) that allow damaged, non-dividing cells to resist programmed cell death. Senescent cells accumulate with aging and secrete the SASP (senescence-associated secretory phenotype) — inflammatory cytokines, matrix metalloproteinases, and growth factors that drive tissue dysfunction. By clearing senescent cells, D+Q reduces SASP-driven chronic inflammation.

Standard Dosing

Research indicates Dasatinib 100 mg + Quercetin 1000-1250 mg orally for 2 consecutive days, repeated every 2-4 weeks (intermittent 'hit-and-run' dosing).

Timing

Take both compounds together on dosing days, with or without food. The 'hit-and-run' approach exploits the fact that senolytic effect occurs rapidly but senescent cells take weeks to re-accumulate. Quercetin bioavailability is improved by fat co-ingestion.

Cycle Duration

Ongoing intermittent cycles. Long-term safety data in healthy populations is limited. Typically used in periodic courses (e.g., 2 days per month for 3-6 months, then reassess).

Side Effects

• GI discomfort, nausea, diarrhea (both compounds)
• Fluid retention and peripheral edema (dasatinib)
• Headache
• Thrombocytopenia and neutropenia (dasatinib — typically mild at senolytic doses)
• Pleural effusion (rare at intermittent dosing; more common with chronic oncology dosing)
• Skin rash

Contraindications

• Active bleeding disorders or thrombocytopenia
• Severe hepatic impairment
• Pulmonary arterial hypertension
• QT prolongation risk or concurrent QT-prolonging drugs
• Pregnancy and breastfeeding
• Active infections (temporary immunosuppression)

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Mechanism

Fisetin is a naturally occurring flavonol (3,7,3',4'-tetrahydroxyflavone) found in strawberries, apples, and persimmons that acts as a senolytic by inhibiting the PI3K/Akt/mTOR survival pathway and BCL-2 family anti-apoptotic proteins in senescent cells. It also activates sirtuin-mediated pathways (SIRT1), reduces NF-kB-driven inflammation, and scavenges free radicals as a direct antioxidant. Fisetin demonstrated the most potent senolytic activity among 10 flavonoids screened in a 2018 study, reducing senescent cell burden in aged mice and extending both healthspan and lifespan markers.

Standard Dosing

Research indicates 20 mg/kg/day for 2 consecutive days as an intermittent senolytic protocol (approximately 1400-2000 mg for a 70-100 kg individual).

Timing

Take with fat-containing meal for improved bioavailability (fisetin is lipophilic with poor water solubility). Liposomal or lipophilic formulations preferred.

Cycle Duration

Intermittent senolytic courses ongoing. Daily low-dose use for antioxidant/anti-inflammatory effects can be continuous.

Side Effects

• GI discomfort at high senolytic doses
• Diarrhea
• Headache
• Generally well-tolerated — no serious adverse events reported in clinical trials to date

Contraindications

• Known hypersensitivity to fisetin or flavonoids
• Pregnancy and breastfeeding (insufficient safety data)
• Active chemotherapy without oncologist coordination

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