https://brain.forever-healthy.org/displ ... ic+Therapy
"Senolytics are agents that selectively induce apoptosis of senescent cells. Fisetin is a flavonoid polyphenol found in many types of fruits and vegetables (Arai et al., 2000) that is believed to act as a senolytic in addition to its numerous other known benefits.
Although natural senolytics are less potent, compared to the targeted senolytics, they have lower toxicity and are thus, likely to be more readily translatable to clinical medicine. This RBA focuses on the risks and benefits of using fisetin as a senolytic rather than its more common use as a supplement.
Key Questions
This risk-benefit analysis seeks to answer the following questions:
- Which health and/or longevity benefits result from the use of fisetin as a senolytic?
- Which risks are involved in the use of fisetin as a senolytic (general and method-specific)?
- What are the potential risk mitigation strategies?
- Which method or combination of methods of using fisetin as a senolytic are most effective?
- Which of the available methods are safe for use?
- What is the best therapeutic protocol available at the moment?"
Main benefits
Fisetin has been shown to decrease senescent cell biomarkers as well as the numbers of senescent cells in a variety of tissues, including ex vivo, human adipose tissue as well as in vivo, in mice.
Main risks
Reduction of senescent cells has been associated with delayed wound healing and an increased level of fibrosis after healing (Demaria et al., 2014). Fisetin was associated with liver toxicity in mice at doses of 223 mg/kg administered over 3 weeks (Sun et al., 2018). There is also the possibility of drug interactions with glucose-lowering drugs such as metformin.
Risk Mitigation Strategies
- Wait to commence therapy until clinical trial data has been published that describes the possible benefits and adverse effects
- Consult your physician before beginning therapy
- Frequency of therapy is to be determined by the results of the senescent cell biomarker lab panel
- Measure baseline senescent cell load biomarkers including SA-β-gal activity, p16Ink4a expression, p21Cip1 expression, and SASP factors: IL-6, IL-8, MCP-1 when possible
- Repeat screening at regular intervals to determine the effectiveness of the therapy, and the appropriateness of the dose
- Measure blood values, liver & kidney function and electrolyte values at regular intervals
- Use caution when combining fisetin with glucose-lowering drugs (monitor blood sugar levels)
- Avoid or use with extreme caution if nonalcoholic fatty liver disease has been diagnosed or is suspected
- Cease therapy if any identifiable adverse effects occur