Dasatinib for Senolytic Therapy — Aging
Tyrosine kinase inhibitor used in combination with quercetin as a senolytic agent to selectively clear senescent cells.
Overview
Dasatinib is a multi-targeted tyrosine kinase inhibitor FDA-approved for chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). In 2015, Mayo Clinic researchers James Kirkland and Tamara Tchkonia demonstrated that dasatinib in combination with quercetin (D+Q) acts as a potent senolytic cocktail — selectively inducing apoptosis in senescent cells while sparing healthy cells. Senescent cells accumulate with aging and secrete a pro-inflammatory senescence-associated secretory phenotype (SASP) that drives tissue dysfunction, chronic inflammation, and age-related disease. Dasatinib targets senescent preadipocytes by inhibiting ephrin B-dependent survival signaling and multiple tyrosine kinases (SRC family, c-KIT, PDGFR), while quercetin targets senescent endothelial cells via BCL-2 family and PI3K/AKT pathway inhibition. The D+Q combination has shown promise in preclinical models for improving physical function, reducing frailty markers, extending healthspan, and treating idiopathic pulmonary fibrosis. A Phase 1 human trial in diabetic kidney disease (n=9) demonstrated reduced senescent cell burden, reduced SASP markers, and improved adipose tissue function after just 3 days of treatment. The senolytic paradigm uses intermittent hit-and-run dosing — short courses separated by weeks — since the goal is to eliminate senescent cells, not maintain continuous drug exposure.
Indications
- FDA-approved: Chronic myeloid leukemia (CML) — daily dosing
- FDA-approved: Philadelphia chromosome-positive ALL
- Investigational: Senolytic therapy (with quercetin) for aging-related conditions
- Investigational: Idiopathic pulmonary fibrosis (D+Q senolytic)
- Investigational: Diabetic kidney disease (senolytic approach)
Mechanism of Action
Dasatinib inhibits SRC family kinases, ephrin B receptors, c-KIT, and PDGFR, disrupting pro-survival signaling in senescent preadipocytes
Dosing
| Compound | Dose | Frequency | Notes |
|---|---|---|---|
| Dasatinib + Quercetin | 100 mg D + 1000 mg Q | 3 consecutive days per month | Senolytic protocol from Kirkland/Tchkonia research |
| Dasatinib + Quercetin | 100 mg D + 1250 mg Q | 2 consecutive days, every 2 weeks x 3 weeks | DKD clinical trial protocol |
| Dasatinib | 100 mg | Once daily (continuous) | FDA-approved CML dose — NOT for senolytic use |
Evidence Grade
GRADE C
Safety & Contraindications
- Myelosuppression: neutropenia, thrombocytopenia, anemia (primarily at oncologic doses)
- Pleural effusion (significant risk at chronic oncologic dosing; unknown risk at senolytic doses)
- Fluid retention and peripheral edema
- GI effects: nausea, diarrhea, vomiting
- QTc prolongation — avoid with other QTc-prolonging drugs
- Pulmonary arterial hypertension (rare, typically chronic use)
- Hepatotoxicity potential — monitor LFTs
- INTERMITTENT senolytic dosing (2-3 days/month) likely carries lower risk than chronic oncologic dosing
- Very limited human safety data at senolytic doses in healthy aging population