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Fisetin is a naturally occurring plant polyphenol from the flavonoid group, similar to quercetin. It is present in many plants, where it acts as a colouring agent. It is also found in many fruits and vegetables, such as strawberries, apples, persimmons, onions, and cucumbers.

It has also been found to be a senolytic compound able to clear senescent cells, at least in vitro studies in a petri dish. The clearance of dysfunctional senescent cells is one of the repair-based approaches proposed by the SENS Research Foundation to prevent or reverse age-related diseases.

Before you jump on the bandwagon

We see this every time a new compound or supplement is in the news: people rush out to buy it before sufficient research has been done. We should be cautious here, and before we spend our hard-earned money on yet another supplement, we should be mindful that there is no evidence that fisetin has a senolytic effect in mice other than in cell cultures.

What happens in in vitro cell culture studies does not always reflect what happens in vivo, as the complexity of a living system can often change how compounds interact. While initial in vitro studies can often be a great indication of the potential of a compound, and indeed is why they are done, the results are not always the same when tested in mice.

We often see studies in which fantastic results are observed during cell culture testing, but they fail utterly when moving to a living environment. This is because biology is complex, and that is why we should be cautious before jumping on a bandwagon.

Interesting research

That said, there is no denying that this research is interesting, although the researchers do not touch upon the senolytic properties of fisetin and its influence on senescent cells in this study. The researchers here show that fisetin, when added to the diet of SAMP8 mice, does delay some of the accelerated aging observed in this particular mouse strain.

The SAMP8 mouse is a mouse model of Alzheimer’s, as it suffers from accelerated aging; it is worth stating at this point that these mice are also not representative of normal aging, so, again, the results should be taken with a pinch of salt.

The team examined levels of specific proteins in the mice related to brain function, responses to stress, and inflammation. They found at 10 months that there were significant differences between the control group and the group of mice given fisetin. Mice not given fisetin experienced impaired cognitive ability during tests as well as increased levels of inflammation and stress. In the mice, they observed that astrocytes and microglia, normally anti-inflammatory, were instead producing excessive levels of inflammation, having become dysfunctional.

The mice given fisetin were different: there was little difference between their behavior, cognitive ability, and inflammatory biomarkers and those of typical 3-month-old untreated mice of the same strain. The researchers also found no evidence of acute toxicity in the fisetin-treated mice, even with high doses of the compound.

Conclusion

At the risk of sounding boring, the take-home here is that more research is needed before a conclusion can be reached. There is no human data and very little data in mice at this point, and it is also unknown if fisetin removes senescent cells in vivo. While it is tempting to experiment with the latest supplement, it is probably a little premature to jump on the bandwagon just yet; just stick to eating strawberries.

CategoryNews, Research
About the author

Steve Hill

Steve serves on the LEAF Board of Directors and is the Editor in Chief, coordinating the daily news articles and social media content of the organization. He is an active journalist in the aging research and biotechnology field and has to date written over 500 articles on the topic as well as attending various medical industry conferences. In 2019 he was listed in the top 100 journalists covering biomedicine and longevity research in the industry report – Top-100 Journalists covering advanced biomedicine and longevity created by the Aging Analytics Agency. His work has been featured in H+ magazine, Psychology Today, Singularity Weblog, Standpoint Magazine, and, Keep me Prime, and New Economy Magazine. Steve has a background in project management and administration which has helped him to build a united team for effective fundraising and content creation, while his additional knowledge of biology and statistical data analysis allows him to carefully assess and coordinate the scientific groups involved in the project. In 2015 he led the Major Mouse Testing Program (MMTP) for the International Longevity Alliance and in 2016 helped the team of the SENS Research Foundation to reach their goal for the OncoSENS campaign for cancer research.
  1. March 24, 2019

    Fisetin could have potential negative effects on antiaging through its effects of shortening telomeres by causing cells to go through more cell divisions. Maybe it wouldn’t be detrimental if the enzyme telomerase were activated at the same time to renew the telomere numbers or counteract the shortening effect, but I also came across this one animal study on fisetin that no one seems to be mentioning. Fisetin in mice at 1 micromolar blood levels actually shortened telomeres after a period of time in normal mice. Those mice which were subjected to increased oxidative stress did not show reduced telomeres relative to the control with oxidative stress. But if we think about how so many antiaging enthusiasts take a lot antioxidants, then if they don’t have a higher than normal amount of oxidative stress maybe Fisetin could shorten telomeres. Since some cells go through increased divisions every 30 to 60 days to replace senescent cells, or maybe when taking a senolytic like fiestin it would happen sooner, it makes sense what a lot of people are saying to just take it for a short time, like 5 days at 500 to 700 mg per day to get the senolytic blood levels. Then maybe at the same time or shortly thereafter take telomerase upregulating nutraceuticals such as high dose melatonin, Ginkgo biloba, milk thistle, and cycloastragenol/ astragaloside-4. Even tocotrienols, vitamin D, and Omega 3 upregulate telomerase. I found studies on all of those, though the shortcomings admittedly are that many are just cell or animal studies, though the ones for Vit D and Omega 3 were actually human studies. It still is a gamble unless people take blood tests of their telomere end cap numbers which is available now from testing labs for those willing to pay the money. Otherwise it is a shot in the dark.
    Here is the excerpt about Fisetin in the conclusion section:
    Chronic fisetin treatment of HF at physiological concentrations resulted in shorter telomeres compared to control cells, indicating reduced telomere stability and enhanced biological aging of these cells. Under the assumption that it is healthy, fisetin is often added to nutritional supplements at relatively high concentrations. Since the biological effects of regular consumption of high doses of fisetin (and also flavonoids in general) are not known, thorough safety evaluation is warranted with respect to these nutritional supplements. Chronic minocycline treatment also enhanced telomere shortening. This implies that precaution should be taken when minocycline is subscribed as a chronic treatment.
    However, under conditions of chronic oxidative stress, both fisetin and minocycline appeared to reduce the rate of telomere shortening. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3844163/
    part of abstract:
    “Therefore we evaluated the effect of chronic PARP-1 inhibition (by fisetin and minocycline) in human fibroblasts (HF) cultured under normal conditions and under conditions of chronic oxidative stress, induced by tert-butyl hydroperoxide (t-BHP). Results showed that PARP-1 inhibition under normal culturing conditions accelerated the rate of telomere shortening. However, under conditions of chronic oxidative stress, PARP-1 inhibition did not show accelerated telomere shortening. We also observed a strong correlation between telomere length and subtelomeric methylation status of HF cells. We conclude that chronic PARP-1 inhibition appears to be beneficial in conditions of chronic oxidative stress but may be detrimental under relatively normal conditions.”

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