Goal
Reduce senescent cell burden to extend healthspan and lifespan
Problem
Cellular senescence and age-related functional decline
Concept Summary
Fisetin, a plant flavonoid, acts as a senolytic compound that selectively induces apoptosis in senescent cells, thereby decreasing inflammatory signaling, restoring tissue homeostasis, and extending median and maximum lifespan in aged mice. The compound is also being explored for neuroprotective and anti-aging benefits in humans.
Detailed Description
The technology comprises (1) identification of fisetin as a potent senolytic through in-vitro screening of flavonoids, (2) demonstration of its efficacy in aged wild-type and progeroid mice via intermittent oral dosing, showing reduced senescence markers, improved tissue pathology, and lifespan extension, and (3) extraction methods for large-scale production of high-purity fisetin from plant sources (e.g., Toxicodendron succedaneum, boxwood, smoke trees) using alkaline soaking, ethanol extraction, and crystallization steps. The senolytic mechanism is a "hit-and-run" induction of apoptosis in senescent fibroblasts, endothelial cells, and adipocytes, while sparing proliferating cells.
Principles
- Senolytic activity
- Selective apoptosis of senescent cells
- Anti-inflammatory effect
- Antioxidant activity
Scientific Domains
Materials
- Fisetin (C15H10O6)
- Sodium hydroxide (NaOH)
- Ethanol (C2H5OH)
- Limewater (Ca(OH)2 solution)
- Macroporous resin
- n-Butyl alcohol
- Ethyl acetate
- Water
Mechanisms of Action
- Induction of apoptosis in senescent cells via inhibition of pro-survival pathways
- Modulation of inflammatory cytokine release
- Antioxidant scavenging of reactive oxygen species
Applications
- Anti-aging therapeutics
- Neurodegenerative disease treatment
- Senolytic drug development
Claimed Performance
In aged wild-type mice, intermittent fisetin treatment restored tissue homeostasis, reduced age-related pathology, and extended median and maximum lifespan; senescent markers were reduced in multiple tissues.
Experimental Evidence
Mouse studies (EBioMedicine 2018) demonstrated lifespan extension and senescent cell reduction; human adipose tissue explants showed cell-type specific senolytic activity; multiple peer-reviewed papers report cognitive and physiological benefits in SAMP8 mice.
Replication Status
Results published in peer-reviewed journals (EBioMedicine 2018; J Gerontol A 2018) and supported by several patents on fisetin extraction; no independent large-scale clinical replication reported yet.
Limitations
- Optimal human dosing not yet established
- Long-term safety data limited
- Efficacy demonstrated primarily in animal models
