🌿 Quercetin — The Flavonol Senolytic & Senescence-Associated Secretory Phenotype (SASP) Fighter

Introduction: A Common Flavonol with Uncommon Potential

Quercetin is one of the most abundant dietary flavonoids, belonging to the flavonol subclass. It is widely distributed in the plant kingdom and consumed regularly through fruits, vegetables, tea, wine, and herbs. Average daily intake in Western diets ranges from 10–100 mg, with higher intakes possible in plant-rich eating patterns.

Over the past decade, quercetin has gained significant attention in aging and cancer research for its ability to selectively eliminate senescent cells (senolytic activity) and suppress the senescence-associated secretory phenotype (SASP) — the pro-inflammatory, pro-tumorigenic secretome that senescent cells emit. It also exhibits broad anti-inflammatory, antioxidant, anti-cancer, and immune-modulating effects through multiple molecular targets.

Natural Dietary Sources of Quercetin

Quercetin occurs in foods primarily as glycosides (bound to sugar molecules), with the aglycone (free) form present in smaller amounts. Bioavailability is moderate (2–20% absorbed), improved by dietary fat and the presence of other flavonoids. Top natural sources include:

• Capers — Highest known source (~180–230 mg/100 g)
• Onions (especially red/yellow, outer layers) — ~20–50 mg/100 g
• Apples (with skin) — ~4–10 mg/100 g
• Berries (elderberries, lingonberries, cranberries, blueberries) — 5–30 mg/100 g
• Kale, broccoli, asparagus, spinach — 5–15 mg/100 g
• Green and black tea — ~2–5 mg per cup
• Red wine, buckwheat, citrus fruits, parsley, cilantro — variable but meaningful amounts

Consuming quercetin-rich foods (especially onions, apples with skin, and berries) provides a steady, food-based intake with synergistic cofactors (e.g., other polyphenols) that enhance absorption and effects.

Key Mechanisms of Action

1. Senolytic Activity — Selective Clearance of Senescent Cells

Senescent cells accumulate with age and secrete a harmful mix of cytokines, chemokines, growth factors, and proteases (the SASP), which drives chronic inflammation, tissue dysfunction, and cancer progression. Quercetin is one of the first identified senolytics — compounds that preferentially induce apoptosis in senescent cells while sparing healthy ones.

Mechanisms include:

• Inhibition of anti-apoptotic pathways (Bcl-2 family proteins)
• Suppression of SASP via NF-κB and PI3K/AKT/mTOR inhibition
• Synergy with dasatinib (D+Q protocol) — widely studied in animal models and early human trials for clearing senescent cells in skin, adipose, and lung tissue

2. Anti-Cancer & Chemopreventive Effects

Quercetin shows multi-target anticancer activity in preclinical models:

• Induction of apoptosis and cell cycle arrest (p53, p21 upregulation)
• Inhibition of proliferation pathways (PI3K/AKT, mTOR, Wnt/β-catenin)
• Anti-angiogenic and anti-metastatic effects (VEGF, MMP-2/9 downregulation)
• Epigenetic modulation (HDAC inhibition, DNA methylation changes)
• Enhancement of chemotherapy/radiotherapy sensitivity

Human observational data links higher dietary quercetin intake to reduced risk of lung, colorectal, and prostate cancers, though randomized trials are limited.

3. Anti-Inflammatory & Immune Modulation

Quercetin potently inhibits:

• NF-κB activation and pro-inflammatory cytokines (IL-1β, IL-6, TNF-α)
• Mast cell degranulation and histamine release (useful in allergies)
• TLR signaling and inflammasome activation

It also modulates immune balance, supporting T-cell function while reducing excessive inflammation.

4. Neuroprotection & Metabolic Benefits

Quercetin crosses the blood-brain barrier and protects neurons via Nrf2 activation, antioxidant effects, and reduction of neuroinflammation. It improves insulin sensitivity, reduces adipose inflammation, and shows promise in metabolic syndrome and NAFLD models.

Bioavailability & Practical Use

Native quercetin has moderate bioavailability (~2–20%), improved by:

• Consuming with dietary fat (e.g., olive oil, nuts)
• Food matrix (onions/apples contain cofactors)
• Enhanced formulations (quercetin phytosomes, aglycone supplements, or quercetin dihydrate)

Typical supplemental doses in studies: 500–1,000 mg/day (often with bromelain or vitamin C for synergy). Senolytic protocols (D+Q) use short “hit-and-run” dosing (e.g., 1,000–1,500 mg quercetin + dasatinib intermittently). Long-term high-dose safety is not fully established; food sources are safest for daily use.

Potential Interactions, Cautions & Who Should Consult a Doctor

• Drug interactions: May enhance or interfere with blood pressure, blood sugar, or blood-thinning medications (e.g., metformin, warfarin, antihypertensives).
• Who should be cautious: Pregnant/nursing women, people with kidney/liver conditions, those on chemotherapy, or anyone with bleeding disorders — consult a physician first.
• Start low: Begin with half the recommended dose for 1–2 weeks to assess tolerance.
• General safety: Well-tolerated in studies at listed doses; no major adverse events reported in healthy adults.

Always speak with your healthcare provider before adding supplements, especially if you take prescription medications or have chronic health conditions.

Conclusion & Future Directions

Quercetin is a versatile, food-derived flavonol with compelling preclinical evidence as a senolytic, SASP suppressor, anti-inflammatory, and multi-target anticancer agent. Its natural abundance in onions, capers, apples, and berries makes it easy to incorporate into a longevity-focused diet, while enhanced formulations offer higher-dose potential.

Ongoing human trials are evaluating quercetin (often as D+Q) for senescent cell clearance in age-related conditions (osteoarthritis, idiopathic pulmonary fibrosis, Alzheimer’s) and as an adjuvant in cancer. For now, regular dietary intake remains one of the safest, most evidence-supported ways to benefit from this multifunctional compound.

📺 Quercetin in the News & Research (YouTube Videos)

Here are high-quality, science-based videos covering quercetin’s senolytic effects, SASP suppression, cancer chemoprevention, natural sources, and longevity research:

• Quercetin as a Senolytic – Dr. James Kirkland (Mayo Clinic) — Leading senolytics researcher discusses D+Q protocol and human trials.
• Quercetin: The Most Important Supplement? – Dr. Rhonda Patrick — In-depth look at mechanisms, sources, and evidence for aging/cancer.
• Senolytics: Dasatinib + Quercetin (D+Q) – The Science Explained — Clear overview of senescent cell clearance and clinical progress.
• Quercetin Benefits: Anti-Aging, Cancer Prevention, Allergies – Dr. Berg — Practical guide to food sources and supplementation.
• Supplements for Cancer Support: Curcumin, EGCG, Quercetin, Resveratrol & More — Discussion on quercetin’s role in cancer gene regulation and support.

📚 References (Quercetin / Senolytics / SASP)

1. Xu M, Pirtskhalava T, Farr JN, et al. Senolytics improve physical function and increase lifespan in old age. Nature Medicine. 2018;24(8):1246-1256. doi:10.1038/s41591-018-0092-9
2. Zhu Y, Tchkonia T, Pirtskhalava T, et al. The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs. Aging Cell. 2015;14(4):644-658. doi:10.1111/acel.12344
3. Hickson LTJ, Langhi Prata LG, Bobart SA, 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;47:446-456. doi:10.1016/j.ebiom.2019.08.069
4. Justice JN, Nambiar AM, Tchkonia T, et al. Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study. EBioMedicine. 2019;40:554-563. doi:10.1016/j.ebiom.2018.12.052
5. Li Y, Yao J, Chang M, et al. Quercetin, Inflammation and Immunity. Nutrients. 2016;8(3):167. doi:10.3390/nu8030167
6. Miles SL, McFarland M, Niles RM. Molecular and physiological actions of quercetin: implications for cancer prevention and therapy. Current Topics in Medicinal Chemistry. 2016;16(29):3297-3308. doi:10.2174/1568026616666160607093953
7. Anand David AV, Arulmoli R, Parasuraman S. Overviews of Biological Importance of Quercetin: A Bioactive Flavonoid. Pharmacognosy Reviews. 2016;10(20):84-89. doi:10.4103/0973-7847.194044