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This risk-benefit analysis is part of Forever Healthy's "Rejuvenation Now" initiative that seeks to continuously identify potential rejuvenation therapies and systematically evaluate their risks, benefits, and associated therapeutic protocols to create transparency.

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.

This RBA 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?  

Impatient readers may choose to skip directly to Section 6 for the conclusion and tips on practical application. 

The RBA has been prepared based on the principles outlined in A Comprehensive Approach to Benefit-Risk Assessment in Drug Development ( Sarac et al., 2012 ). 

A literature search was conducted on Pubmed and the Cochrane Library using the search terms shown in Table 1 . Titles and abstracts of the resulting studies were screened and relevant articles downloaded in full text. The references of the full-text articles were manually searched in order to identify additional trials that may have been missed by the search terms.

Because of the small number of papers available on the topic, we also searched for studies in which fisetin was found to influence any of the 6 known Senescent Cell Anti-Apoptotic Pathways (SCAPs).