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Fisetin is a plant-derived flavonoid studied for its potential to support healthy aging by targeting senescent cells — sometimes called “zombie cells.” These damaged cells stop dividing but don’t die. Instead, they accumulate in tissues over time and release inflammatory compounds that may contribute to age-related decline.
Because of its senolytic activity, fisetin has gained attention as one of the most promising natural compounds for supporting cellular health and longevity.
Research suggests fisetin may:
Help clear senescent (zombie) cells
Support healthy aging pathways
Provide antioxidant protection
Promote cognitive resilience with aging
Support skin and tissue health
While human clinical trials are still ongoing, preclinical studies have shown that fisetin influences several biological pathways associated with aging and cellular stress.
What Is Fisetin?
Fisetin is a flavonol — a type of plant polyphenol found in small amounts in fruits and vegetables such as strawberries, apples, grapes, onions, and persimmons. In plants, fisetin helps protect against environmental stress.
In the human body, fisetin has been studied for two primary properties:
Senolytic activity (helping clear senescent cells)
Antioxidant effects (helping protect cells from oxidative stress)
These dual actions are what make fisetin especially interesting in longevity research.
Figure 1: Best fisetin food sources. Source: Rahmani et al (2022). Molecules; 27(24), 9009; Licence: CC BY 4.0.
While these senolytic foods supply relatively high amounts of fisetin compared to other foods in the diet, they don’t supply anywhere near the amount of fisetin researchers are using to support a senolytic benefit.
Top Fisetin Benefits
1. Supports Clearance of Senescent Cells
Cellular senescence is one of the hallmarks of aging. As we get older, senescent cells accumulate in tissues and secrete inflammatory signaling molecules collectively known as the SASP (senescence-associated secretory phenotype). This environment may disrupt normal tissue function.
Fisetin has been shown in preclinical studies to selectively target senescent cells by interfering with their pro-survival pathways, encouraging them to undergo apoptosis (programmed cell death). By helping reduce the burden of lingering zombie cells, fisetin may support healthier tissue function over time.
2. Promotes Healthy Aging and Longevity Pathways
Beyond clearing senescent cells, fisetin influences several cellular pathways associated with longevity — including mTOR, AMPK, and SIRT1 signaling. These pathways play roles in cellular repair, energy regulation, and stress resistance.
Fisetin has also been shown to support autophagy (the cellular “cleanup” process) and mitophagy (the removal of damaged mitochondria), both of which are critical for maintaining cellular quality control as we age.
3. Provides Antioxidant Protection
Oxidative stress increases with age and can damage DNA, proteins, and cell membranes. Fisetin acts as both a direct antioxidant — scavenging reactive oxygen species — and an indirect antioxidant by supporting the body’s natural defenses, including glutathione production.
By helping maintain redox balance, fisetin may contribute to cellular resilience and overall tissue health.
How Fisetin Works as a Senolytic
The most robust type of evidence that an intervention works comes from high-quality scientific studies in humans in which the effect of a given compound is compared to that of a placebo control. These are known as randomized placebo-controlled clinical trials. There are several ongoing clinical trials of this type for fisetin as a senolytic, but they haven’t been completed yet.
Another type of evidence comes from preclinical studies which are carried out in research animals or in vitro (i.e., using cells or fragments of tissues in which pathways and mechanisms can be studied). Although these do not provide the robust evidence of working in humans that a placebo-controlled trial would, they may provide proof of mechanism and proof of principle, i.e., they may show that a given compound targets a certain process or pathway of interest in such a way that qualifies them as a senolytic. That’s the case with fisetin. Despite the lack of completed clinical trials, preclinical and in vitro studies such as the ones described above have provided proof of mechanism and proof of principle that fisetin works as a senolytic to support healthier aging [5–7,18].
Fisetin vs. Quercetin: Which Is Better?
Quercetin and fisetin are two of the most studied senolytic compounds. Quercetin, like fisetin, is flavonoid polyphenol. Fisetin and quercetin are closely related molecules with very similar chemical structures and color—they are both yellow in color. Therefore, it is highly likely that they have many similar properties and actions. Both fisetin and quercetin are thought to have both senolytic and senomorphic potential [note: senomorphics are compounds that neutralize the senescence-associated secretory profile (SASP) of senescent cells] [23].
In a study that screened a panel of flavonoid polyphenols for senolytic activity using senescent murine and human fibroblasts, it was found that, of the 10 flavonoids tested, which included quercetin, fisetin was the most potent senolytic [5]. In this study, fisetin was senolytic when used on its own, while quercetin has, in most studies, been combined with another compound in order to produce a senolytic outcome. And, fisetin may be active as a senolytic in tissues where quercetin is less active or inactive, such as adipose tissue. This combination of reasons gives some advantage to fisetin, but both have shown great potential in preclinical studies. And as with fisetin, clinical trials using quercetin (usually combined with another senolytic compound) are still ongoing. So it’s early to tell with confidence which is better, but since fisetin appears to be the more versatile senolytic compound when used on its own, the edge currently goes to it.
For now, based on the available evidence, it seems they’re both good in ways that may complement each other. Because they are both promising senolytic compounds and because we believe their actions may be complementary, we included both fisetin and quercetin in Qualia Senolytic.
Fisetin in Qualia Senolytic
Fisetin supplements differ in their source, extraction processes, and purity levels, all of which can influence their quality. We use fisetin obtained from the stems of Rhus succedanea (Japanese fruit wax tree), the primary source of fisetin for dietary supplements. We use a high-purity standardized extract containing not less than 98% fisetin.
We chose the recommended serving of fisetin based on the fisetin dosage most commonly being used in clinical research to support senolytic functions. As an example, in several ongoing studies sponsored by the Mayo Clinic, fisetin is being dosed at 20 mg per kg body weight daily, orally for two consecutive days (ClinicalTrials.gov identifier NCT03675724, NCT03430037, NCT04476953, NCT04771611, NCT03325322). The 1400 mg fisetin serving in Qualia Senolytic would correspond to the daily amount being used in these studies for a person weighing approximately 155 pounds (70 kg). Our recommended serving selection also took into account that Qualia Senolytic contains several other ingredients that would be expected to be complementary with fisetin. For example, luteolin, which is also included in Qualia Senolytic, has been shown to complement fisetin in supporting healthy immune signaling [24,25]*
Fisetin Bioavailability: What You Should Know
Most polyphenols—fisetin included—are relatively poorly absorbed through the gut barrier. But science has been showing more and more that they can also act locally inside the gut and may exert effects on gut microbiota and through the gut-brain axis as well. What if some of the functional health benefits of a polyphenol occur because of the poor bioavailability and the interaction with our gut microbiomes? If the polyphenol is made too bioavailable, these benefits may be lessened or missed entirely. Because of this consideration, our science team puts much more weight on scientific studies evaluating body and brain responses over bioavailability alone. And, big picture, despite evidence suggesting poor bioavailability there are a lot of studies suggesting beneficial support for the brain and body even from poorly absorbed polyphenols.
The data on the bioavailability of fisetin is a main reason that the Mayo Clinic chose to use a high dose of fisetin in their senolytic studies, and why we are recommending the 1400 mg/day serving of fisetin (which for a person of average weight matches the Mayo serving size). In published animal studies of fisetin, oral fisetin in this human-equivalent range has supported the management of senescence cells, which is the main outcome we care about (not bioavailability). We think the recommended serving included in Qualia Senolytic is sufficient taking into account the data on fisetin’s low bioavailability, but we would not be as confident that the amount we've seen in other supplements claiming a senescent cell benefit (often 100 mg of fisetin and sometimes a bit more) would be enough to provide the intended support.*
How to Take Fisetin
For those looking to integrate fisetin into a broader health regimen, consider pairing it with other longevity-promoting supplements and a balanced lifestyle. Fisetin's antioxidant and senolytic properties make it a strong candidate for use in one’s regimen, particularly in combination with a balanced diet rich in fruits and vegetables, regular exercise, and other lifestyle habits aimed at promoting cellular health and longevity. This holistic approach can help amplify the benefits of fisetin, supporting overall well-being and healthy aging.
Can You Take Fisetin Every Day?
In a study in which fisetin was administered to 10 participants, after a month of placebo, at a dose of 200 mg/day (2 x 100 mg/day) for a month, followed by another month of 800 mg/day (2 x 400 mg/day) fisetin, no serious adverse effects were reported [26]. A few mild to moderate side effects occurred in the fisetin group, including upset stomach, nausea, fatigue, and headaches, but these were also observed in the placebo group. So there was no evidence of significant side effects that could be attributed to fisetin taken daily for two months. Still, this was a study with a very small number of participants, so conclusions must be cautious.
But one of the features of Qualia Senolytic is that it is not something that needs to be taken every day; it is a 2-day a month supplement. The approach to intake recommended (i.e., take for two consecutive days followed by 28 days before the next intake cycle) is consistent with the intermittent intake approaches being used in some ongoing studies, and more broadly with the approach to supplementing with fisetin for senolytic purposes being recommended by experts in the healthy aging community the Qualia science team has been in communication with.*
*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.
References
[1]C. López-Otín, M.A. Blasco, L. Partridge, M. Serrano, G. Kroemer, Cell 186 (2023) 243–278.
[2]D. Muñoz-Espín, M. Serrano, Nat. Rev. Mol. Cell Biol. 15 (2014) 482–496.
[3]B.G. Childs, M. Gluscevic, D.J. Baker, R.-M. Laberge, D. Marquess, J. Dananberg, J.M. van Deursen, Nat. Rev. Drug Discov. 16 (2017) 718–735.
[4]N.S. Gasek, G.A. Kuchel, J.L. Kirkland, M. Xu, Nat. Aging 1 (2021) 870–879.
[5]M.J. Yousefzadeh, Y. Zhu, S.J. McGowan, L. Angelini, H. Fuhrmann-Stroissnigg, M. Xu, Y.Y. Ling, K.I. Melos, T. Pirtskhalava, C.L. Inman, C. McGuckian, E.A. Wade, J.I. Kato, D. Grassi, M. Wentworth, C.E. Burd, E.A. Arriaga, W.L. Ladiges, T. Tchkonia, J.L. Kirkland, P.D. Robbins, L.J. Niedernhofer, EBioMedicine 36 (2018) 18–28.[6]N. Khan, D.N. Syed, N. Ahmad, H. Mukhtar, Antioxid. Redox Signal. 19 (2013) 151–162.
[7]O. Elsallabi, A. Patruno, M. Pesce, A. Cataldi, S. Carradori, M. Gallorini, Molecules 27 (2022).
[8]S. Verma, A. Singh, A. Kumari, C. Tyagi, S. Goyal, S. Jamal, A. Grover, J. Recept. Signal Transduct. Res. 37 (2017) 391–400.
[9]K. Sundarraj, A. Raghunath, L. Panneerselvam, E. Perumal, Nutr. Cancer 73 (2021) 2502–2514.
[10]S. Jia, X. Xu, S. Zhou, Y. Chen, G. Ding, L. Cao, Cell Death Dis. 10 (2019) 142.
[11]C.-J. Liou, C.-H. Wei, Y.-L. Chen, C.-Y. Cheng, C.-L. Wang, W.-C. Huang, Cell. Physiol. Biochem. 49 (2018) 1870–1884.
[12]W. Yang, Z.-K. Tian, H.-X. Yang, Z.-J. Feng, J.-M. Sun, H. Jiang, C. Cheng, Q.-L. Ming, C.-M. Liu, Food Chem. Toxicol. 134 (2019) 110824.
[13]Y. Sun, H. Qin, H. Zhang, X. Feng, L. Yang, D.-X. Hou, J. Chen, Food Nutr. Res. 65 (2021).
[14]S. Kim, K.J. Choi, S.-J. Cho, S.-M. Yun, J.-P. Jeon, Y.H. Koh, J. Song, G.V.W. Johnson, C. Jo, Sci. Rep. 6 (2016) 24933.
[15]S. Singh, A.K. Singh, G. Garg, S.I. Rizvi, Life Sci. 193 (2018) 171–179.
[16]H. Ding, Y. Li, S. Chen, Y. Wen, S. Zhang, E. Luo, X. Li, W. Zhong, H. Zeng, CNS Neurosci. Ther. 28 (2022) 247–258.
[17]I.M.N. Molagoda, A.M.G.K. Athapaththu, Y.H. Choi, C. Park, C.-Y. Jin, C.-H. Kang, M.-H. Lee, G.-Y. Kim, Antioxidants (Basel) 10 (2021).
[18]P. Maher, Genes Nutr. 4 (2009) 297–307.
[19]A. Currais, C. Farrokhi, R. Dargusch, A. Armando, O. Quehenberger, D. Schubert, P. Maher, J. Gerontol. A Biol. Sci. Med. Sci. 73 (2018) 299–307.
[20]J. Das, R. Singh, S. Ladol, S.K. Nayak, D. Sharma, Exp. Gerontol. 138 (2020) 111006.
[21]K. Takaya, T. Asou, K. Kishi, Biogerontology (2023).
[22]C. Kubo, M. Ogawa, N. Uehara, Y. Katakura, Front Cell Dev Biol 8 (2020) 566617.
[23]S. Romashkan, H. Chang, E.C. Hadley, J. Gerontol. A Biol. Sci. Med. Sci. 76 (2021) 1144–1152.
[24]A. Kim, J.-M. Yun, J. Med. Food 20 (2017) 782–789.
[25]M. Hytti, D. Szabó, N. Piippo, E. Korhonen, P. Honkakoski, K. Kaarniranta, G. Petrovski, A. Kauppinen, J. Nutr. Biochem. 42 (2017) 37–42.
[26]K.S. Hodgin, E.K. Donovan, S. Kekes-Szabo, J.C. Lin, J. Feick, R.L. Massey, T.J. Ness, J.W. Younger, Int. J. Environ. Res. Public Health 18 (2021).
