Quercetin (regular) — The Foundational Flavonoid Senolytic

Quercetin is a naturally occurring flavonoid that exerts its longevity-promoting effects through multiple pathways. It acts as a senolytic by transiently disabling pro-survival networks (SCAP pathways) that defend senescent cells against apoptosis, particularly targeting the PI3K/AKT pathway and Bcl-xL. Beyond its senolytic activity, quercetin is a potent antioxidant and anti-inflammatory agent that inhibits the NF-κB pathway, reducing the production of pro-inflammatory cytokines. It also activates AMPK and sirtuins (such as SIRT1), which promote mitochondrial biogenesis and metabolic regulation.

Quercetin has been studied in humans primarily in combination with dasatinib (D+Q) as a senolytic therapy. A pilot study in patients with diabetic kidney disease showed that a 3-day course of D+Q significantly reduced senescent cell burden in adipose tissue and decreased circulating SASP factors within 11 days. Another first-in-human open-label pilot study in patients with idiopathic pulmonary fibrosis (IPF) demonstrated that intermittent D+Q treatment improved physical function, though it did not significantly alter pulmonary function. Long-term human longevity trials of quercetin alone are lacking.

500–1,000 mg/day is the most commonly studied range in human trials. Often taken in divided doses (e.g., 500 mg twice daily). For senolytic protocols, it is typically used intermittently (e.g., 1,000 mg/day for 3 consecutive days per month) in combination with dasatinib. Absorption is generally poor, so it is often taken with dietary fats or in liposomal/phytosome formulations to improve bioavailability.

Generally well-tolerated at standard doses (up to 1,000 mg/day). High doses or long-term use may cause headaches, nausea, or tingling in the extremities, and could potentially stress the kidneys; it should be used with caution in individuals with kidney disease. Quercetin can inhibit CYP3A4 and other cytochrome P450 enzymes, potentially interacting with medications such as blood thinners, antibiotics, and certain cardiovascular drugs.

Key Papers