Fisetin for Alzheimer's Disease
Also known as: 3,3',4',7-Tetrahydroxyflavone
Fisetin is a potent senolytic and neuroprotective flavonoid that targets cellular senescence driving AD neurodegeneration.
Mechanism of Action
Fisetin selectively eliminates senescent cells through PI3K/Akt/mTOR pathway modulation. It activates Nrf2 antioxidant defense, inhibits GSK3β to reduce tau phosphorylation, promotes neurogenesis through ERK signaling, and maintains glutathione levels.
General mechanism: Bioactive flavonoid. Senolytic (PI3K/Akt/mTOR), Nrf2 activator, GSK3β inhibitor, anti-inflammatory, pro-apoptotic in cancer cells.
Current Evidence
AFFIRM trial studying fisetin for Alzheimer's (Phase II). Preclinical models show cognitive improvement and reduced neuroinflammation. Senolytic effects confirmed in aged mice with improved cognitive function.
Clinical Status: Phase II (AFFIRM trial). Available as supplement. Senolytic trials ongoing.
Safety Profile
Very safe. Low oral bioavailability. Liposomal formulations being developed. No significant side effects.
Key Research Questions
- Can fisetin senolytics clear senescent cells from AD brain?
- Does fisetin's dual senolytic-neuroprotective action outperform single-mechanism approaches?