Dasatinib + Quercetin Protocol: Mayo Clinic Senolytic Evidence
Expert Summary
The D+Q pilot study (Xu et al., Nature Medicine 2018) was the first human trial to demonstrate that senolytics reduce senescent cell burden in vivo. Nine patients with idiopathic pulmonary fibrosis (IPF) received 3 intermittent doses of dasatinib 100 mg + quercetin 1,000 mg. Post-treatment adipose biopsies showed 35% reduction in p16+p21-positive senescent cells, and circulating SASP factors decreased significantly.
Key Facts
- Protocol design: Dasatinib 100 mg oral + quercetin 1,000 mg oral, taken on days 1, 3, and 5 of a 21-day period. The intermittent ("pulsed") dosing avoids dasatinib's continuous dosing side effects while providing senolytic windows.
- Mechanism synergy: Dasatinib targets src kinase survival pathways in epithelial senescent cells; quercetin targets BCL-2/BCL-XL in adipocyte senescent cells. The combination covers a broader range of senescent cell types than either agent alone.
- Adipose tissue response: Adipose tissue biopsies showed the most dramatic senescent cell reduction (35%), consistent with its high baseline senescent cell burden in aged/diseased individuals and the adipocyte-targeting specificity of quercetin.
- Physical function improvement: In the D+Q frailty trial (PMID: 31542391), gait speed, grip strength, and 6-minute walk distance improved significantly vs placebo. These are validated frailty markers with strong mortality prediction.
- IPF progression: A phase 2 trial in IPF patients showed D+Q reduced fibrosis progression markers and improved lung function in some participants, consistent with the mechanistic role of senescent cells in fibrosis pathology.
- Access: Dasatinib requires a prescription in most countries. Longevity physicians and forward-thinking internists may prescribe it off-label for aging-related indications. Quercetin is available OTC.
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Frequently Asked Questions
How often is the D+Q protocol repeated?
The original trial used 3 doses over 5 days (intermittent). Subsequent protocols in clinical trials range from quarterly to biannual repetition. Monthly repetition is used in some longevity clinics.
What are the risks of dasatinib in healthy people?
Dasatinib's side effect profile in CML patients (pleural effusion, thrombocytopenia, cardiovascular events) is driven by daily continuous dosing. Intermittent senolytic dosing (3 days every 3 months) has a dramatically reduced side effect profile. Baseline platelet count and cardiac evaluation are standard precautions.
Can quercetin alone achieve D+Q-like results?
Natural quercetin alone has more modest senolytic activity than the D+Q combination. However, phytosome quercetin combined with fisetin approaches the D+Q evidence base for natural senolytic protocols.
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: preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease. EBioMedicine. 2019. PMID: 31542391