Dasatinib + Quercetin / Fisetin (Senolytics)
Dasatinib + Quercetin & Fisetin — the first senolytics in human trials: how "zombie cell" clearance really works, and what the data show

Class: blend
Synonyms: D+Q (Dasatinib + Quercetin)
Fisetin (a separate flavonoid senolytic)
"senolytics" (from senescence + lytic)
Function tags: senescent-cell clearance (senolytic)
anti-inflammatory / anti-SASP
longevity / healthspan (investigational)
age-related disease (many indications, exploratory)
Overall evidence grade: A
WADA prohibited: no
Last updated: 2026-07-13

In brief: Dasatinib+Quercetin (D+Q) and Fisetin are the first and best-known senolytics — drugs that selectively kill senescent "zombie" cells, which accumulate with age and pump out an inflammatory secretome (SASP) implicated in 40+ age-related conditions. They were discovered by a clever hypothesis (Kirkland/Mayo, 2015): senescent cells cling to life via anti-apoptotic survival pathways, so blocking those makes them self-destruct while normal cells are spared. Dasatinib is an FDA-approved leukemia drug; quercetin (apple-peel bitterness) and fisetin (most concentrated in strawberries) are natural flavonoids — fisetin being the most potent and safest-profiled. A key trick is "hit-and-run" dosing — brief pulses (about two days every couple of weeks) that clear senescent cells while dodging a chemo drug's sustained toxicity. Their decisive distinction in this register: they actually reached human trials — the first to demonstrably reduce senescent cells in people (2019, diabetic kidney disease). But across Alzheimer's, osteoporosis, and frailty studies, the clinical outcomes have been mixed and modest — real cell-clearing, few clear wins, small underfunded trials, and missing biomarkers. The honest read: the most clinically-advanced senolytics — genuinely in humans, genuinely clearing zombie cells — but not yet proven to deliver the healthspan benefits the mouse data promise. Powerful proof-of-concept; unfinished clinical story.

## Identity the archetypal **senolytics** — agents that **selectively kill senescent ("zombie") cells.** **Dasatinib (D)** is an **FDA-approved tyrosine-kinase inhibitor** (a leukemia drug since 2006); **Quercetin (Q)** is a **natural flavonoid** (the bitterness in apple peels); the two are used **together (D+Q)** for synergy. **Fisetin** is a **separate natural flavonoid** (most concentrated in strawberries) — the **most potent senolytic flavonoid** found and the **safest-profiled** of the three. None is a peptide; they're grouped as the register's **real-world senolytic** entry. ## Mechanism (as proposed) (Zhu et al., *Aging Cell* 2015, Kirkland/Tchkonia). The insight: **senescent cells, like cancer cells, depend on anti-apoptotic "survival" pathways** (SCAPs) to avoid dying from their own toxic inflammatory secretions. **Block those survival pathways** and the senescent cells **self-destruct** — while normal cells, which don't depend on them, survive. Bioinformatics mapped the survival networks; **D+Q were the prototype drugs** that came out. This made them the **first senolytics ever identified.**
- **The players and their mechanisms:** **Dasatinib** kills senescent cells by inhibiting **Src/tyrosine kinases** (dependence-receptor apoptosis); **Quercetin** hits **Bcl-xL, PI3K, and mTOR** — and because each covers **different senescent cell types** (D favors senescent preadipocytes, Q favors senescent endothelial cells), **the combination clears more than either alone.** **Fisetin**, screened as the **top of 10 flavonoids** (Yousefzadeh/Kirkland, *EBioMedicine* 2018), reduced senescence markers across tissues and **extended lifespan in old mice.**
- **⚠ The "hit-and-run" insight (why a cancer drug becomes tolerable):** senolytics need only **brief pulses** — famously **~2 days of dosing every couple of weeks**, not continuous use. Because the senescent cells are killed and stay gone for a while, this **intermittent schedule** achieves the effect while **avoiding the sustained toxicity** dasatinib causes as a daily chemotherapy. "The dose makes the poison" — short-burst senolytic use has looked **safe and well-tolerated** in trials so far.
- **⚠ The human translation (the decisive contrast):** unlike most longevity compounds here, **senolytics have genuinely entered the clinic.** The **first human evidence of senescent-cell clearance** came in 2019 (Hickson et al., *EBioMedicine*, diabetic kidney disease) — D+Q measurably **reduced senescent cells in people.** Numerous trials followed (Alzheimer's, osteoporosis, frailty, IPF, sepsis, PAD, osteoarthritis). **But the clinical *outcomes* so far are mixed and modest** (see evidence): a **Phase 1 Alzheimer's trial (SToMP-AD)** found **"very few significant results and no suggestion of effectiveness"**; a **Mayo osteoporosis Phase 2** **missed on the whole group** (with a burden-dependent subgroup signal); frailty (fisetin, AFFIRM-LITE) has been **"mixed."** The senescent-cell-clearing is real; the **clinical payoff is still unproven.**

Evidence grades by outcome:
outcome: Senescent-cell clearance in humans (the proof-of-concept)
grade: B
base: Hickson 2019 (diabetic kidney disease): D+Q measurably reduced senescent cells in people
caveat: The genuine landmark — first human senolytic clearance; but clearance ≠ clinical benefit
outcome: Lifespan/healthspan (animal)
grade: A
base: D+Q and fisetin extend healthspan/lifespan across mouse models; fisetin top of 10 flavonoids
caveat: Strong mouse data — the usual "mouse ≠ human" gap applies
outcome: Alzheimer's / cognition (human)
grade: F
base: SToMP-AD Phase 1: "very few significant results, no suggestion of effectiveness"; STAMINA pilot (n=12) feasibility only
caveat: Tested — no cognitive benefit shown; safety/feasibility only
outcome: Osteoporosis / bone (human)
grade: D
base: Mayo Phase 2: missed on whole group; burden-dependent subgroup signal
caveat: Negative primary; hypothesis that baseline senescent burden dictates response
outcome: Frailty / physical function (human)
grade: C
base: Fisetin AFFIRM-LITE: mixed, some positive physical-function trends
caveat: Preliminary/mixed; ongoing
outcome: Safety (intermittent dosing)
grade: B
base: Short "hit-and-run" pulses safe/well-tolerated in trials to date
caveat: Flavonoids benign; dasatinib is a real chemo drug — off-label self-use is hazardous

Legal status:
region: INT
status: See note
note: - Dasatinib — an approved prescription cancer drug (leukemia). Senolytic/longevity use is off-label and requires medical oversight (it's a real chemotherapeutic).
- Quercetin / Fisetin — natural flavonoids sold as dietary supplements (widely legal); found in foods. No approved senolytic/anti-aging indication.
- Your region · EU · US — no senolytic use is approved; all longevity use is investigational/off-label.
- Gray-market note: quercetin and fisetin are freely sold supplements (and cosmetic ingredients); dasatinib is a potent prescription chemo drug that should never be self-administered for longevity.

Cosmetic claims:

Note: The "zombie cell" killers that actually reached the clinic — the honest counterpoint to FOXO4-DRI. This closing entry is the register's real-world senolytic case, and its whole value is the contrast with FOXO4-DRI (#67): where that peptide has zero human data, Dasatinib+Quercetin (D+Q) and Fisetin have been through dozens of human trials. Three threads: (1) they were the first senolytics ever discovered — via a clever hypothesis, not random screening; (2) they clear senescent "zombie" cells using a short "hit-and-run" dosing that sidesteps a cancer drug's toxicity; (3) crucially, the human results so far are mixed and modest — real senescent-cell clearance, but few clear clinical wins. Dasatinib is a prescription cancer drug; quercetin and fisetin are natural flavonoids.
Status note: the field's need: adequately-powered Phase 2/3 trials with validated senescence biomarkers — many ongoing (sepsis, PAD, osteoarthritis); the open question is whether human clearance finally translates to clinical benefit

Sources:
Zhu Y, et al. The Achilles' heel of senescent cells: from transcriptome to senolytic drugs. Aging Cell 2015 (D+Q discovery; SCAP hypothesis).
Kirkland JL, Tchkonia T. Senolytic drugs: from discovery to translation. J Intern Med 2020 (D, Q, Fisetin, Navitoclax as first senolytics).
Hickson LJ, et al. Senolytics decrease senescent cells in humans… EBioMedicine 2019 (first human clearance, diabetic kidney disease).
Yousefzadeh MJ, et al. Fisetin is a senotherapeutic that extends health and lifespan. EBioMedicine 2018 (top flavonoid; mouse lifespan).
Human outcome trials: SToMP-AD Phase 1 (Alzheimer's, few significant results); Mayo osteoporosis Phase 2 (whole-group miss); STAMINA pilot (MCI, n=12, feasibility); AFFIRM-LITE (fisetin, frailty, mixed). (No approved senolytic indication; clinical benefit unproven as of 2026.)