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quercetin

Properties1
aliases2-(3, 4-dihydroxyphenyl)-3, 5, 7-trihydroxychromen-4-one, quercetin dihydrate, quercetol

16 min read

Quercetin

A dietary flavonol found at high concentrations in capers, red onions, apples, tea, and leafy greens. Quercetin is the senolytic half of the canonical D+Q regimen (dasatinib + quercetin), the first senolytic combination demonstrated to reduce senescent-cell burden in living humans 1. Structurally similar to fisetin — quercetin has an additional hydroxyl group at ring position 5, giving the molecule 5 OH groups versus fisetin’s 4. The extra hydroxyl increases antioxidant potency but does not appear to materially alter the core senolytic mechanism.

Identity

  • PubChem CID: 5280343
  • InChIKey: REFJWTPEDVJJIY-UHFFFAOYSA-N
  • ChEMBL: CHEMBL50
  • CAS: 117-39-5
  • Class: flavonol (flavonoid subclass)
  • Molecular formula: C15H10O7
  • Molecular weight: 302.23 g/mol
  • IUPAC name: 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxychromen-4-one
  • Structural difference from fisetin: additional 5-OH on the A-ring; fisetin lacks the 5-OH position

Mechanism of action

Senolytic activity — SCAP disruption

Zhu et al. 2015 performed transcriptomic analysis of senescent human umbilical vein endothelial cells (HUVECs) and mouse embryonic fibroblasts (MEFs), mapping upregulated pro-survival pathways that protect senescent cells from their own pro-apoptotic SASP 2. They identified these as SCAPs (Senescent-Cell Anti-Apoptotic Pathways) and screened candidate compounds for selective elimination of cells dependent on them.

Quercetin’s SCAP targets in HUVECs 2:

  • BCL-xL — quercetin reduces BCL-xL expression in senescent HUVECs (via EFNB1/BCL-xL network node); siRNA against EFNB1 or BCL-xL is selectively lethal to senescent HUVECs
  • (removed: PI3KCD-in-HUVECs claim) — Per senolytics verifier round (Zhu 2015 Fig 1D vs 1E/G), PI3KCD/PI3Kδ is preadipocyte-selective, not a HUVEC SCAP. Quercetin’s broad PI3K-class inhibition contributes to its preadipocyte coverage in the D+Q combination, but PI3KCD is not the dominant HUVEC mechanism — that’s BCL-xL + EFNB1.

Dasatinib’s complementary SCAP targets — ephrin receptor (EFNB/EPH) kinase signaling and serine protease inhibitors (serpins, including PAI-2/SERPINB2) — cover senescent preadipocytes (mesenchymal type), which quercetin alone does not efficiently eliminate 2. Serpins are preadipocyte SCAP nodes targeted by dasatinib, not a primary quercetin target. The two agents together achieve broader cell-type coverage than either alone.

Cell-type selectivity: Quercetin is most active against senescent endothelial cells (HUVECs) in vitro. In vivo, D+Q combination clears senescent cells across multiple tissues and cell types, but quercetin as monotherapy has incomplete coverage 2. needs-replication — monotherapy vs combination cell-type specificity has not been fully mapped in vivo.

Other documented activities

  • ROS scavenging: direct antioxidant via polyphenol electron donation; inhibits lipid peroxidation
  • Anti-inflammatory: suppresses NF-κB-mediated transcription of TNFα, IL-1β, IL-6; inhibits COX and LOX enzymes; blocks TLR4/MyD88/PI3K complex formation 3. NLRP3 inflammasome inhibition is reported in other literature but is not addressed in Li 2016 — remove attribution to that claim here. unsourced — NLRP3 claim needs a specific primary citation
  • HSP90 inhibition: reported at supraphysiological concentrations; may contribute to proteotoxic stress in senescent cells
  • Bcl-xL / Bcl-2 binding: reported in silico and in some biochemical assays, but evidence is weaker than for navitoclax-class compounds; not the primary mechanism contradictory-evidence

Dietary sources and typical intake

SourceQuercetin content (mg/100 g fresh weight)
Capers (raw)234
Red onions~32–50
Apples (skin)~4–8
Green tea (brewed)~2–4 per 200 mL
Broccoli~3

Average Western dietary intake is estimated at 10–30 mg/day — orders of magnitude below doses used in senolytic trials (~500–1,000 mg/day). unsourced — precise intake estimates vary widely by method and population; cross-check against a dietary survey citation.

Pharmacokinetics

Oral bioavailability is poor and highly variable, which is the primary translational challenge.

  • Absorption: Quercetin aglycone is absorbed in the small intestine, but most dietary quercetin is present as glycosides (quercetin-3-glucoside, quercetin-3-rutinoside). Deglycosylation by gut enzymes and microbiota determines effective absorption. Glycoside form significantly affects uptake kinetics 3.
  • Conjugation: Extensively conjugated to glucuronides and sulfates in intestinal epithelium and liver. Most circulating quercetin in plasma is in conjugate form; biological activity of conjugates is debated.
  • Plasma half-life: 3.5 h (average terminal half-life, human oral) 3. The reported range across studies is 11–28 h for some metabolites, but the terminal half-life of quercetin itself averages 3.5 h. Peak plasma concentrations occur ~0.5–1 h post-ingestion. The comparison to fisetin’s half-life in prior text was not sourced in Li 2016 and is removed here. unsourced — cross-compound PK comparison needs a dedicated PK study citation.
  • Protein binding: >99% bound to albumin in plasma.
  • Food effects: Co-ingestion with dietary fat increases absorption in overweight adults.

The short half-life is consistent with a “hit-and-run” senolytic mechanism — brief exposure above threshold is sufficient to trigger apoptosis in SCAP-dependent senescent cells, not requiring sustained plasma levels. This motivates the intermittent pulsed dosing schedule used in clinical trials (3 consecutive dosing days per week for 3 weeks in the Justice 2019 IPF protocol; a single 3-day course in the Hickson 2019 DKD protocol).

dose-response-unclear — Dose translation from mice to humans is uncertain. Trials use 500–1,000 mg/day quercetin (typically quercetin dihydrate or encapsulated form), but tissue exposure depends on formulation, food intake, and microbiome composition.

Effects on aging hallmarks

HallmarkEffectEvidence
cellular-senescenceD+Q reduces circulating senescent cell markers (p16, p21) in adipose tissue in humans1
cellular-senescenceD+Q clears senescent cells in progeroid and aged mice; reduces senescent cell burden and SASP2
chronic-inflammationQuercetin reduces NF-κB-driven SASP cytokines (IL-6, IL-1β, TNFα) in vitro3

Dose-response and preclinical evidence

StudyOrganismnDoseRouteScheduleEffect
Zhu 2015 2HUVECs and preadipocytes (in vitro)N=4–5 replicatesQ alone: optimal 10 μM (HUVECs), 20 μM (preadipocytes); D+Q combination: 100–200 nM D + 15–30 μM QIn media3 daysQuercetin alone selectively eliminated senescent HUVECs (50% viability reduction at 10 μM vs. no effect on proliferating HUVECs); dasatinib alone preferentially eliminated senescent preadipocytes; combination (D+Q) achieved selective killing of both senescent preadipocytes and HUVECs
Zhu 2015 2Aged C57BL/6 mice (24-month-old males)N=8/group5 mg/kg D + 50 mg/kg QOral gavageSingle dose (cardiac/vascular experiments)Reduced senescent cell burden; improved left ventricular ejection fraction and vascular reactivity; N=6–9/group for inguinal fat senescent cell clearance
Zhu 2015 2Ercc1−/Δ progeroid miceN=7–8/group5 mg/kg D + 50 mg/kg QOral gavageWeekly from 4–6 weeks of age; euthanized 10–12 weeksExtended healthspan; reduced composite aging score; delayed onset of kyphosis, tremor, ataxia, gait disorders; improved bone parameters and intervertebral disk GAG content

Extrapolation assessment (preclinical to human):

DimensionStatus
SCAP pathway conserved in humans?yes — pathway identified directly in human HUVECs 2
Senescent cell clearance in humans?yes (limited) — p16/p21 reduction in adipose biopsy 1
Replicated in healthy older humans?no — trials to date in disease populations only; no healthy aging trial published

Human clinical evidence

Justice 2019 — IPF open-label pilot (n=14) 4

First-in-human trial of D+Q as a senolytic. Enrolled 14 patients with idiopathic pulmonary fibrosis (IPF), an age-related fibrotic lung disease with known senescent cell accumulation. Protocol: dasatinib 100 mg/day + quercetin 1,250 mg/day (250 mg capsules × 5/day) for 3 consecutive days per week for 3 weeks (9 total treatment days). 100% retention (14/14 completed) with no drug discontinuation.

Primary endpoints were retention rate and completion rate for planned clinical assessments — feasibility outcomes, not efficacy. Secondary functional endpoints showed statistically and clinically significant improvements:

  • 6-minute walk distance (6MWT) increased by 21.5 m (p=0.012)
  • 4-meter gait speed improved by 0.12 m/s (p=0.024)
  • Timed 5-times sit-to-stand decreased by 2.2 s (p=0.013)
  • Short Physical Performance Battery (SPPB) score improved (p=0.003)

Pulmonary function (FEV1, FVC) was unchanged, consistent with expectations given the short study duration and progressive nature of IPF. Correlations were observed between functional improvements and changes in SASP markers in plasma (23/48 SASP markers r ≥ 0.50). Limitations: open-label, no placebo arm, n=14, disease population only; study was powered for feasibility, not efficacy.

Hickson 2019 — Diabetic kidney disease pilot (n=9) 1

9 patients with diabetic kidney disease (DKD); mean age 68.7 ± 3.1 years; 7 male, 2 female. Protocol: dasatinib 100 mg/day + quercetin 1,000 mg/day for 3 consecutive days, single course. Abdominal subcutaneous adipose tissue biopsies and attached skin biopsies obtained at Day 0 (baseline) and Day 14 (11 days after completing the last dose of D+Q).

Key findings (Day 14 vs. Day 0):

  • Adipose p16INK4a+ cells reduced by 35% in raw values (p=0.001)
  • Adipose p21CIP1+ cells reduced by 17% in raw values (p=0.009)
  • Adipose SA-βgal+ cells reduced by 62% in raw values (p=0.005)
  • Adipose CD68+ macrophages decreased 28% (p=0.0001) — consistent with senescent-cell-anchored macrophage reduction
  • Circulating SASP factors significantly reduced: IL-1α, IL-6, MMP-9, MMP-12 (all p<0.05)
  • Adipocyte progenitor cell density/time in culture increased 8% (p=0.027), consistent with depletion of senescent and pre-senescent cells limiting replicative potential
  • This was the first human in vivo demonstration that senolytics physically reduce senescent cell burden in a tissue biopsy

Limitations: no control arm, n=9, single-course treatment only, disease population; sample size was set for 80% power to detect a difference of 5% in SA-βgal activity.

Farr 2024 — postmenopausal women, bone metabolism Phase 2 RCT (n=60) 5

The first placebo-controlled D+Q senolytic RCT to publish primary results. Sixty postmenopausal women age ≥70 randomized to intermittent D 100 mg + Q 1000 mg × 2 consecutive days every 4 weeks × 5 cycles (20 weeks) vs placebo. Primary endpoint MISSED: percent change at 20 weeks in CTx (bone resorption) — D+Q −4.1% (IQR −13.2, 2.6) vs control −7.7% (IQR −20.1, 14.3); p=0.611. Secondary P1NP (bone formation) increased significantly at 2 weeks (+16%, p=0.020) and 4 weeks (+16%, p=0.024) but normalized by 20 weeks (−9%, NS). No serious adverse events. Exploratory tertile analysis: women with the highest T-cell p16 mRNA (highest senescent-cell-burden tertile) showed concomitant P1NP +34% (p=0.035), CTx −11% (p=0.049) at 2 weeks, and radius BMD +2.7% (p=0.004) at 20 weeks. The first signal that baseline senescent-cell burden may dictate D+Q response — likely to shape future trial designs around biomarker-stratified enrollment. NCT04313634.

The biomarker companion paper (Farr 2025 Aging Cell) 6 characterizes T-cell p16_variant 5 (one of two p16 protein-coding transcripts at the CDKN2A locus) as a more selective predictor of D+Q response than total p16 (variant 1+5). Variant 5 detection arises later than variant 1+5 in DNA-damage-induced senescence (Week 4 vs Week 1 in vitro), suggesting variant 5 is a marker of established senescent-cell abundance rather than acute senescence induction. A correlated plasma SASP panel performed equivalently in identifying responders and is more clinically tractable than the T-cell assay.

Gonzales 2023 — SToMP-AD Phase 1 (n=5) 7

Open-label proof-of-concept Phase 1 in n=5 early-symptomatic mild AD patients (mean age 76 ± 5 y, 40% female), 12-week dosing with intermittent D 100 mg + Q 1000 mg. Confirmed CNS penetrance of dasatinib (CSF:plasma ratio 0.42–0.92% in 4/5 participants) but quercetin not detected in CSF. Treatment well-tolerated; no early discontinuation. CSF IL-6 and GFAP increased post-treatment (p=0.008, p=0.028); cognitive endpoints unchanged. NCT04063124. The follow-up exploratory biomarker analysis (Garbarino 2025 Neurotherapeutics) 8 reported plasma fractalkine + MMP-7 increases, modest CSF Aβ/tau stability, and PBMC downregulation of pro-inflammatory transcripts (FOS, FOSB, IL1β, IL8, JUN, JUNB, PTGS2). The CSF-undetectable quercetin finding raises the question of whether D+Q’s CNS effects are dasatinib-only or quercetin metabolites (which were not assayed in CSF) drive the brain pharmacology.

Liu 2025 — COIS-01 D+Q + anti-PD-1 Phase 2 in HNSCC (n=51) 9

Phase 2 trial of D+Q + anti-PD-1 neoadjuvant chemoimmunotherapy in head & neck squamous cell carcinoma. Major pathological response 33.3% (95% CI 16.6–54.7%); grade 3–4 AE rate 4.2%. Frames D+Q as an immunosenescence-clearing adjunct enabling checkpoint inhibitor response — a translational application separate from healthspan/aging applications. Mechanistic preclinical work in the same paper (naturally aged + Ercc1-deficient progeroid mice) demonstrates senolytic-mediated reduction of T/B-cell immunosenescence enables anti-PD-1 efficacy. NCT05724329.

Active trials as of 2026-05-08 (CT.gov v2 API)

Six active D+Q senolytic trials (clinical-trials-active: 6):

TrialNCTPhaseStatusnEndpoint
Senolytics in IPF (Justice 2019)NCT02874989Phase 1 pilotCompleted14Retention/completion + functional
Senolytics in DKD (Hickson 2019)NCT02848131Phase 1 pilotCompleted9p16/p21/SA-βgal in adipose biopsy
D+Q in postmenopausal bone (Farr 2024)NCT04313634Phase 2 RCTCompleted60CTx Δ at 20 wk (primary missed)
SToMP-AD Phase 1 (Gonzales 2023)NCT04063124Phase 1Completed5CSF penetrance + safety
Senolytics to Improve Osteoporosis Therapy (SENOSTEO)NCT06018467Phase 2Active, not recruiting~90BMD, bone turnover
D+Q in HIV (SPACE)NCT07144293Phase 2Active, not recruitingTBDPhysical function
Adipose snRNA-seq mappingNCT05653258Phase 2/3RecruitingTBDSenescent adipose populations
SToMP-AD Phase 2 (Alzheimer’s)NCT04685590Phase 2Active, not recruiting~50AD progression
Sequential D+Q+fisetin+temozolomideNCT07025226Early Phase 1RecruitingTBDCancer-context safety
SEN-SURVIVORS (childhood cancer survivors)NCT04733534Phase 2Active, not recruitingTBDFrailty in CCS
COIS-01 D+Q + anti-PD-1 in HNSCC (Liu 2025)NCT05724329Phase 2Reported51Major pathological response

needs-human-replication — As of 2026-05-08, the placebo-controlled D+Q RCT data is limited to a single trial (Farr 2024 n=60 in postmenopausal women) which missed its primary endpoint in the unstratified analysis. The exploratory tertile finding (high senescent-cell-burden subgroup responded) needs confirmatory trials with biomarker-stratified enrollment.

long-term-unknown — No trial has evaluated D+Q safety or efficacy beyond ~20 weeks (Farr 2024 dosing window).

Preclinical safety signal — oligodendrocyte demyelination (Lombardo 2026 PNAS) 10

Naïve young (3–4 mo) and aged (22 mo) C57BL/6J mice treated with D+Q developed significant corpus callosum demyelination vs. vehicle, without overt cell death. In vitro, primary rat oligodendrocyte progenitor cells in differentiation media exposed to D+Q showed reduced MBP and morphological complexity; bulk RNA-seq + IPA implicated ER stress / unfolded-protein-response signaling. The authors propose D+Q-treated oligodendrocytes resemble those in MS lesions and frame the finding as a model of OPC dysfunction. Translational implications for chronic-cycle senolytic dosing in older adults — particularly any cohort with subclinical white-matter pathology — are unresolved. Note that quercetin was undetectable in CSF in Gonzales 2023 SToMP-AD; if the demyelination signal in mice is quercetin-mediated, human CNS exposure may be below threshold, but if dasatinib alone or D+Q-induced peripheral SASP drives it, the human risk could remain. long-term-unknown contradictory-evidence

D+Q regimen — complementarity rationale

The key insight of Zhu 2015 2 was that different senescent cell types rely on different SCAPs:

  • Senescent endothelial cells (HUVECs) → depend on EFNB1/BCL-xL network → quercetin-sensitive (note: PI3KCD is NOT a HUVEC SCAP per Zhu 2015 Fig 1E/G — corrected from earlier framing; PI3KCD is preadipocyte-selective per Fig 1D)
  • Senescent preadipocytes (mesenchymal) → depend on ephrin/EPH receptor kinases + PI3KCD + serpins (PAI-2/SERPINB2) → primarily dasatinib-sensitive (with quercetin’s PI3K-class inhibition contributing)

No single agent covers both populations efficiently. D+Q combines quercetin’s endothelial coverage with dasatinib’s mesenchymal coverage, making the combination more effective in tissues containing mixed senescent cell types (adipose, lung, kidney). This SCAP-complementarity framework generalizes: future senolytic combinations may be rationally designed by matching agents to SCAP profiles of target cell populations.

Classification

  • SENS strategy: ApoptoSENS — senolytic (clears intracellular junk-accumulating or pro-inflammatory senescent cells)
  • Primary hallmark target: cellular-senescence
  • Secondary: chronic-inflammation (via SASP suppression)
  • Clinical category: dietary supplement / investigational drug (D+Q combination under IND)

Comparison with fisetin

AttributeQuercetinFisetin
Structural classFlavonol (5-OH present)Flavonol (no 5-OH)
PubChem CID52803435281614
Primary senolytic targetHUVECs (endothelial)HUVECs + stem/progenitor cells
Human in vivo dataYes — p16/p21 reduction in adipose (n=9)Pending (Phase 2 NCT03675724)
Used as single agent in trials?No — always co-administered with dasatinibYes — Phase 2 as monotherapy
Typical senolytic dose1,000–1,250 mg/day (pulsed 3 days; 1,250 mg/day in Justice 2019, 1,000 mg/day in Hickson 2019)20 mg/kg/day (pulsed 2 days)

Limitations and concerns

  • Polypharmacology: Quercetin interacts with dozens of targets at micromolar concentrations; in vitro senolytic mechanism may differ from in vivo primary mechanism at lower achieved tissue concentrations.
  • CYP enzyme interactions: Quercetin inhibits CYP3A4 and CYP2C8/9 in vitro — potential for drug-drug interactions when combined with dasatinib (itself a CYP3A4 substrate). Clinical significance of this interaction in the D+Q context has not been formally characterized. long-term-unknown
  • Population specificity: Both published human trials enrolled patients with serious diseases (IPF, DKD). Whether senolytic D+Q benefits healthy older adults is extrapolation at this stage.
  • Formulation matters: Quercetin aglycone, quercetin dihydrate, and glycoside forms have different absorption profiles. Trials use quercetin dihydrate; supplement products vary. Dose equivalence across formulations is not established. dose-response-unclear
  • Dasatinib dependency: Most senolytic evidence for quercetin is combination data. Quercetin monotherapy senolytic evidence in vivo is limited to endothelial-rich tissues.
  • Conflict of interest: Mayo Clinic / Kirkland group holds patents on D+Q senolytic uses; several trial investigators are named inventors. Independent replication outside the Mayo network is limited as of 2026; Liu 2025 (Sun Yat-sen) provides the first large-scale independent D+Q clinical evidence in HNSCC, but in a fundamentally different translational frame (immunotherapy adjunct, not aging-rejuvenation).
  • Primary-endpoint failure (Farr 2024): the first placebo-controlled D+Q RCT failed to demonstrate efficacy on its pre-registered primary bone-resorption endpoint. Whether the exploratory tertile-stratified finding represents a real biomarker-conditional effect or a multiple-testing artifact is unresolved; resolution requires a confirmatory adequately-powered biomarker-stratified trial.

Limitations and gaps

Footnotes

Footnotes

  1. hickson-2019-senolytics-diabetic-kidney · n=9 · open-label pilot (no control arm) · model: diabetic kidney disease, age 68.7 ± 3.1 y · D 100 mg/day + Q 1,000 mg/day × 3 days · doi:10.1016/j.ebiom.2019.08.069 · EBioMedicine 2019 ↩ ↩2 ↩3 ↩4

  2. zhu-2015-achilles-heel-senescent-cells · mouse n=6–9/group (aged C57BL/6); n=7–8/group (Ercc1−/Δ progeroid) · in-vitro (HUVEC, preadipocyte, MEF, BM-MSC) + in-vivo (C57BL/6, Ercc1−/Δ mice) · doi:10.1111/acel.12344 · Aging Cell 2015 ↩ ↩2 ↩3 ↩4 ↩5 ↩6 ↩7 ↩8 ↩9 ↩10

  3. li-2016-quercetin-inflammation-immunity · review · model: in-vitro and in-vivo mixed · doi:10.3390/nu8030167 · Nutrients 2016 ↩ ↩2 ↩3 ↩4

  4. justice-2019-senolytics-ipf-pilot · n=14 · open-label pilot (no control arm) · model: stable IPF patients, age 70.8 ± 7.9 y · D 100 mg/day + Q 1,250 mg/day · 3 days/week × 3 weeks · doi:10.1016/j.ebiom.2018.12.052 · EBioMedicine 2019 ↩

  5. Farr JN, Atkinson EJ, Achenbach SJ, et al. “Effects of intermittent senolytic therapy on bone metabolism in postmenopausal women: a phase 2 randomized controlled trial.” Nat Med 2024;30(9):2605–2612 · n=60 (D+Q n=30 / placebo n=30) · randomized double-blind placebo-controlled · primary endpoint p=0.611 (NS) · model: postmenopausal women age ≥70 · D 100 mg + Q 1000 mg × 2 consecutive days every 4 weeks × 5 cycles (20 wk) · doi:10.1038/s41591-024-03096-2 · PMID 38956196 · NCT04313634 ↩

  6. Farr JN, Monroe DG, Atkinson EJ, et al. “Characterization of Human Senescent Cell Biomarkers for Clinical Trials.” Aging Cell 2025;24(5):e14489 · biomarker companion to Farr 2024 · in-vitro DNA-damage timecourse + retrospective biomarker analysis of NCT04313634 cohort · doi:10.1111/acel.14489 · PMID 39823170 ↩

  7. Gonzales MM, Garbarino VR, Kautz TF, et al. “Senolytic therapy in mild Alzheimer’s disease: a phase 1 feasibility trial.” Nat Med 2023;29(10):2481–2488 · n=5 · open-label proof-of-concept · model: early-symptomatic mild AD, mean age 76 ± 5 y · D 100 mg + Q 1000 mg × 2 consecutive days every 14 days × 6 cycles (12 wk) · CSF dasatinib detected in 4/5 (CSF:plasma ratio 0.42–0.92%); quercetin not CSF-detectable · doi:10.1038/s41591-023-02543-w · PMID 37679434 · NCT04063124 (SToMP-AD) ↩

  8. Garbarino VR, Palavicini JP, Melendez J, et al. “Evaluation of exploratory fluid biomarkers from a phase 1 senolytic trial in mild Alzheimer’s disease.” Neurotherapeutics 2025;22(4):e00591 · biomarker follow-up to Gonzales 2023 · paired t-tests on CSF/plasma/urine analytes pre/post · doi:10.1016/j.neurot.2025.e00591 · PMID 40274471 · NCT04063124 ↩

  9. Liu N, Wu J, Deng E, et al. “Immunotherapy and senolytics in head and neck squamous cell carcinoma: phase 2 trial results.” Nat Med 2025;31(9):3047–3061 · n=51 · COIS-01 Phase 2 single-arm trial · D+Q + anti-PD-1 neoadjuvant chemoimmunotherapy · 33.3% major pathological response (95% CI 16.6–54.7%) · grade 3–4 AEs 4.2% · doi:10.1038/s41591-025-03873-7 · PMID 40855191 · NCT05724329 (COIS-01); preceding NCT04718415 (OOC-001) ↩

  10. Lombardo ER, Pijewski RS, Lustig JT, et al. “Senolytic treatment induces oligodendrocyte dysfunction and demyelination in the corpus callosum.” Proc Natl Acad Sci U S A 2026;123(12):e2524897123 · in-vivo (C57BL/6J young 3–4 mo + aged 22 mo) + in-vitro (primary rat OPCs) · D+Q produced significant CC demyelination without cell death; transcriptomic ER-stress / UPR signature in OPCs · doi:10.1073/pnas.2524897123 · PMID 41843680 ↩

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