Dasatinib + Quercetin: The First Clinically Proven Senolytic Combination
Expert Summary
The D+Q protocol stands as the single most evidence-backed senolytic intervention in human medicine. The Xu et al. (2018) Nature Medicine paper demonstrated: measurable reduction in p16+p21-positive senescent cells in adipose tissue biopsies, reduction in circulating SASP factors (IL-6, MMP-3, MMP-9), and improvement in physical function (walking speed, chair stand, stair climbing) in patients with idiopathic pulmonary fibrosis.
Key Facts
- Mechanism synergy: Dasatinib inhibits ephrin receptors and src-family kinase survival signals specifically upregulated in senescent epithelial cells. Quercetin inhibits BCL-2/BCL-XL and PI3K/AKT specifically upregulated in senescent adipocytes. Together, they cover two distinct senescent cell survival pathways.
- Pilot study design: 9 patients with IPF (a fibrotic lung disease strongly linked to cellular senescence). Dasatinib 100 mg + quercetin 1,000 mg oral × 3 days over a 3-week period. Open-label, no placebo control.
- Biomarker results: p16INK4A mRNA in skin: -67%. p21: -25%. Circulating MMP-3: -27%. MMP-9: -37%. IL-6: -40%. These are the most specific senolytic biomarkers available in human studies.
- Physical function: Gait speed +50%. 4-meter walk test improved significantly. Chair stand count improved. These functional improvements in a debilitating disease are clinically meaningful.
- Subsequent trials: Multiple Phase 2 trials have followed: diabetic kidney disease (DKD), Alzheimer's, frailty in older adults. All report consistent senescent cell reduction and functional improvements.
- Protocol frequency in longevity use: For healthy aging (not disease), most longevity physicians recommend quarterly cycles: dasatinib 100 mg + quercetin 1,000 mg for 2 consecutive days every 3 months.
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Frequently Asked Questions
How do I access dasatinib for longevity purposes?
Dasatinib is a prescription medication (Sprycel®, Bristol-Myers Squibb). In most countries, prescription requires physician evaluation. Longevity medicine practitioners, internists, and some gerontologists may prescribe it off-label for aging indications. Aging.ai and similar directories list longevity physicians.
What monitoring is required with D+Q?
CBC (platelet count monitoring for thrombocytopenia risk), liver function tests, and cardiac evaluation (ECG for QTc prolongation) are standard pre-treatment assessments. Repeat CBC after the first cycle is recommended.
Is D+Q safe for people without disease?
The safety profile of intermittent D+Q (2–3 days per quarter) in healthy aging individuals appears favorable, but no large safety trial has been conducted in this population specifically. The risk-benefit calculation favors caution without physician oversight.
Scientific References
- Xu M et al. Senolytics improve physical function and increase lifespan in old age. Nature Medicine. 2018. PMID: 29988130
- Hickson LJ et al. Senolytics decrease senescent cells in humans. EBioMedicine. 2019. PMID: 31542391