What is the dasatinib + quercetin senolytic protocol?

Short Answer: The D+Q protocol uses dasatinib 100mg + quercetin 1000mg for 3 consecutive days per month to selectively kill senescent cells. It's the most clinically studied senolytic regimen with trials in kidney disease, pulmonary fibrosis, and Alzheimer's.

Evidence Level: moderate

Detailed Answer

Developed by James Kirkland at Mayo Clinic, the D+Q senolytic protocol targets complementary anti-apoptotic pathways in senescent cells. Dasatinib (a tyrosine kinase inhibitor, FDA-approved for leukemia) targets Src, Abl, and c-Kit kinases that senescent cells depend on for survival. Quercetin (a flavonoid) inhibits BCL-2, PI3K, and serpine survival pathways. Together, they target 6+ independent survival nodes. The 'hit-and-run' protocol (3 days on, ~28 days off) works because: (1) senescent cells die within hours of exposure, (2) new senescent cells take weeks to accumulate, (3) brief exposure minimizes chronic drug side effects. Clinical trials: diabetic kidney disease (NCT02848131) showed reduced senescent cell markers; IPF and Alzheimer's trials ongoing. Side effects during 3-day dosing include GI upset, fatigue, and dasatinib-related fluid retention. CBC monitoring is recommended.

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