Fisetin — Polyphenol flavonoid — dietary compound with senolytic and senomorphic properties, CD38 inhibitor
Fisetin is a natural flavonoid found in strawberries, apples, persimmons, and onions. Senolytic mechanism: inhibits pro-survival SCAPs in senescent cells via multiple targets — BCL-2/Bcl-xL inhibition (anti-apoptotic proteins upregulated in senescent cells), PI3K/AKT pathway suppression, and p53/p21 pathway modulation. Additional mechanisms: (1) Potent CD38 inhibition — elevates NAD+ levels by reducing CD38-mediated NAD+ consumption; (2) Anti-inflammatory — inhibits NF-κB and AP-1 pathways, reduces SASP (Senescence-Associated Secretory Phenotype) cytokines; (3) Neuroprotective — reduces oxidative stress and promotes neurotrophic factor expression; (4) Anti-diabetic — improves insulin sensitivity via AMPK activation. Fisetin's senolytic potency exceeds quercetin by ~2-fold in some preclinical models but is lower than dasatinib for adipocyte senescence.
نظرة عامة
هذه الصفحة جزء من مكتبة المركّبات المُصنَّفة بالأدلة في Hormonaly. جميع الادعاءات السريرية مرتبطة بمصادر علمية مُحكَّمة عبر خط أنابيب التحقق المزدوج للاستشهادات.
فئة المركّب
Polyphenol flavonoid — dietary compound with senolytic and senomorphic properties, CD38 inhibitor
آلية العمل
Fisetin is a natural flavonoid found in strawberries, apples, persimmons, and onions. Senolytic mechanism: inhibits pro-survival SCAPs in senescent cells via multiple targets — BCL-2/Bcl-xL inhibition (anti-apoptotic proteins upregulated in senescent cells), PI3K/AKT pathway suppression, and p53/p21 pathway modulation. Additional mechanisms: (1) Potent CD38 inhibition — elevates NAD+ levels by reducing CD38-mediated NAD+ consumption; (2) Anti-inflammatory — inhibits NF-κB and AP-1 pathways, reduces SASP (Senescence-Associated Secretory Phenotype) cytokines; (3) Neuroprotective — reduces oxidative stress and promotes neurotrophic factor expression; (4) Anti-diabetic — improves insulin sensitivity via AMPK activation. Fisetin's senolytic potency exceeds quercetin by ~2-fold in some preclinical models but is lower than dasatinib for adipocyte senescence.
الوضع التنظيمي
NOT FDA approved for any indication. Generally Recognized As Safe (GRAS) as a food component. Sold as dietary supplement. No IND for longevity approved.
مستوى الأدلة
C — AFFIRM-LITE Phase 1 pilot (Hanson et al. 2020, n=40 older adults with frailty, fisetin 20 mg/kg × 2 days): significant reduction in plasma p21 (senescence marker) and adipose tissue senescent cell counts (p<0.05). Alzheimer's Phase 2 trial (NCT03675724) ongoing. No large Phase 3 RCT as of 2024. Preclinical data very robust.