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 it does 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, where the complexity of a living system can often change how compounds interact. Whilst 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 where 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 for that reason why we should be cautious before jumping on the bandwagon.
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 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 another story: there was little difference between their behaviour, cognitive ability, or 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 at high doses of the compound.
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. Whilst it is tempting to experiment with the latest supplement, it is probably a little premature to jump on the bandwagon just yet and just stick to eating strawberries.