Quercetin (phytosome) — The Natural Senolytic and Flavonoid

Quercetin is a naturally occurring dietary flavonoid that exerts pleiotropic effects on cellular aging pathways. It acts as a senolytic primarily by inhibiting the PI3K/AKT survival pathway and downregulating anti-apoptotic proteins (such as Bcl-xL), which allows senescent cells to undergo apoptosis. Additionally, quercetin is a potent antioxidant and anti-inflammatory agent that inhibits the NF-κB pathway, thereby reducing the secretion of senescence-associated secretory phenotype (SASP) factors. It also activates AMPK and SIRT1, mimicking some effects of caloric restriction and promoting mitochondrial biogenesis and metabolic homeostasis.

Quercetin has been studied in humans primarily for its anti-inflammatory and metabolic effects, showing modest benefits in reducing blood pressure and systemic inflammation. In the context of longevity, its most notable human data comes from pilot trials of the dasatinib plus quercetin (D+Q) senolytic protocol. A 2019 trial in patients with diabetic kidney disease demonstrated that a brief course of D+Q significantly decreased senescent cell burden in adipose tissue (Hickson et al., 2019). Subsequent small trials have explored D+Q in idiopathic pulmonary fibrosis and osteoporosis, though large-scale, long-term human longevity data for quercetin monotherapy remains limited.

250–1,000 mg/day is the most studied range in humans. The phytosome formulation (quercetin bound to sunflower phospholipids) is typically dosed at 250–500 mg once or twice daily, taken with a fat-containing meal to maximize absorption. When used as a senolytic in the 'hit-and-run' D+Q protocol, quercetin is often dosed at 1,000 mg/day alongside dasatinib for 2–3 consecutive days per month.

Quercetin is generally well-tolerated at standard doses (up to 1,000 mg/day) for up to 12 weeks. Mild adverse effects can include headache, upset stomach, or tingling in the extremities. Because quercetin inhibits CYP3A4 and other cytochrome P450 enzymes, it can interact with a wide range of medications, potentially increasing their blood levels. Long-term safety data beyond a few months is not well established, and high doses should be used with caution in individuals with kidney disease.

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