Sebastian Fisetin was found to reduce senescent cells in fat tissue as well. There is really only 1 study on Fisetin as a senolytic. They looked at several possible polyphenols, and fisetin was so much more efeective than even quercetin (alone) that they focused the study on it. You can google the study - Fisetin is a senotherapeutic that extends health and lifespan by Matthew J. Yousefzadeh, Yi Zhu, [...], and Laura J. Niedernhofer.  

They went into Phase 2 clinical trials after this study, and are currently researching it on humans. You can find those studies by going to clinicaltrials.org and searching fisetin. The first, and a couple since, have set dosage to 20mg/kg body weight for 2-3 days in a row per a month. The fisetin is in a capsule with peg400 and a couple other things to increase absorption, as it is not water soluble. That specific capsule is not commercially available, so some here take Bioperine to increase absorption. I have taken a CoQ10 supplement with bioperine, and it upset my stomach, so I just take my fisetin with a meal with fat or with some omega 3 fish oil liquid that I often take. I just take the capsules as they are where some here will directly mix the fisetin powder with olive oil or some other oil. I would just try it, and remember that the best therapeutics have few side effects, so hopefully you won't feel much. I get a little extra tired. My husband says he feels sore muscles like after lifting weights, but he also had severe sepsis, so he has a lot of cellular inflammation from which to recover. He feels less sore now than when first taking it after the sepsis. My uncle said that just the fisetin according to the 20mg/kg for 2 days a month helped his arthritis significantly so his fingers hurt much less. Good luck! I am 41, I have taken fisetin for about 3 years or so. I mostly notice some reduction of fine lines in my skin and the cover of a fee moles. However, as my friends are aging, they are beginning to notice that I am aging slower than they are, so I think it may be doing something. The next 10 years from 40 to 50 is really the time to notice as aging speeds up. My runner friends all look young as well, so don't forget some good exercise to keep you healthy and promote autophagy.

JGC Thank you for your fast reply and all the effort you are making

Fairy8i8 I really appreciate this detailed description!! Thank you very much.Only 1 question left : Does it make sense to take F and Q ? Together or alterning or maybe just concentrate solely on F ? Sebastian 

JGC I agree. Because clinical studies haven't been done with the 2 together, it would just be self experimentation. The nice thing about these plant compounds is that they are well studied in other applications and don't seem to have serious negative effects, even at high doses.

JGC and Sebastian, If you would want to take 1gm of Fisetin and 1 gm of Quercetin, I suspect you could leave off the Quercetin if you increase the Fisetin to 2gm.  The reason I say this is that I feel that, at the least, Quercetin might be considered to be sacrificial and extend the effect of Fisetin.  Both F and Q inhibit CYP3A4 activity in a dose dependent manner.  If you have plenty of Fisetin and are not concerned with the cost perhaps you could just bump up the quantity of Fisetin that you are using.  I would also recommend mixing with olive oil and either adding a goodly amount of ground black pepper or some piperene.  I have not seen any information that indicates whether you should take the piperene an hour before, or if you should just take it with the rest of the dose at the same time.  I do it at the same time.   The tests with Dasatinib that I have seen have all been done with Quercetin.

I just did another protocol this week as follows.  I wanted to do both the Dasatinib + Q and the Fisetin + Q instead of doing two separate protocols.  What I ended up doing was taking 100mg of Dasatinib with 500mg of Quercetin in the morning, either before or after I had eaten.  In the evening, on an empty stomach, I took 1500mg of Fisetin and 1000mg of Quercetin all mixed in olive oil with a couple of 10mg pills of bioperine (piperene).  I did this for 3 days in a row.  (I am 69 and about 175kg)

The reason I separated them like this is that I did not want to potentiate the effect of the Dasatinib as I am somewhat leery of getting too high a dose of that, but I wanted to potentiate the Fisetin/Quercetin so that it was absorbed better. 

With this protocol the only real side effects were some headache from the Dasatinib, and some slightly loose stools on the fourth day rather than the all day diarrhea that I had experienced earlier after 2 doses of Dasatinib at 200mg with bioperine...

Dan Nave According to the rep at Sabinsa, Bioperine should be taken at the same time as the Quercetin, the reason being that the piperine will only be active for about 15 minutes after ingested.

chuck stanley In my mind this is the best site for senence treatment https://senolyticstreatment.com/

Van Yes, absolutely the best site, with the most relevant studies! And if its been a while, its well worth the re-read!

@JGC did you see chuck stanley's comment about the timing of Bioperine ingestion?

JGC Very interesting. I will ask the manufacturer to explain the contradiction. I think that a significant portion of Bioperine sales are for use in compounding with bioflavonoids, so the efficacy of simultaneous ingestion is crucial.  

JGC Correct me if I am wrong, but isn't the enzyme in question, and the action we are looking for, in the intestine?  How are we testing this if it is given intravenously?

JGC and Dan Nave This clarifies the mechanism: "The mechanism of action  responsible for the bioavailability enhancing effect of Bioperine® is because a small amount of piperine stimulates the release of catecholamines, thermogenic hormones whose activity is made possible by the presence of cyclic adenosine monophosphate (cAMP) . The thermogenic effect has been localized in the epithelial cells of the intestine that increase the absorption of nutrients. However, the catecholamine-mediated thermogenic response is relatively short. Therefore, the window of absorption has a narrow temporal scope. These thermogenic properties may explain how a minimal amount of BioPerine® can produce such a powerful effect on the uptake of serum nutrients"

JGC Piperine acts as a bioenhancer both in the Gastrointestinal tract and in the liver and in othter metabolic processes responsible for the elimination of substances:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3634921/

From: Bioavailability enhancers of herbal origin: An overview:

" 6.1. Mechanism of action of piperine
Different mechanisms for the bioenhancer activity of piperine have been proposed including DNA receptor binding, modulation of cell signal transduction and inhibition of drug efflux pump[29].

In general, it inhibits drug metabolizing enzymes, stimulates absorption by stimulating gut amino acid transporters, inhibits the cell pump responsible for drug elimination from cells and inhibits intestinal production of glucuronic acid.

It may increase the absorption of drug in the GIT, or inhibit enzymes responsible for drug metabolism, especially in the liver when the drug passes through the liver after absorption from GIT. Oral administration of piperine in rats strongly inhibited the hepatic arylhydrocarbon hydroxylase and UDP-glucuronyltransferase activities[30].

Another study demonstrates that piperine modifies the rate of glucuronidation by lowering the endogenous UDP-glucuronic acid content and also by inhibiting the transferase activity[31].

Piperine inhibits human P-glycoprotein and cytochrome P450 3A4 (CYP3A4)[32]. Both the proteins contribute to a major extent to first-pass elimination of many drugs.

Some of the metabolizing enzymes inhibited or induced by piperine include CYP1A1, CYP1B1, CYP1B2, CYP2E1, CYP3A4 etc. Most of the drugs metabolized by these enzymes will therefore be influenced by bioenhancers.

Some other suggested mechanisms include making target receptors more responsive to drugs, acting as receptors for drug molecules, increasing GIT vasculature by vasodilation to increase absorption of drugs, modulation of the cell membrane dynamics to increase transport of drugs across cell membranes[33].

JGC  What you write should be about optimal, at least according to what the research  can tell us now. 

There is an obvious advantage of using piperine, this since it makes it possible to use exact doses every time. But when it comes to apoptosis and cell cycle arrest, black pepper has other advantages. In theory the other effects could be beneficial in a senolytic treatment.  

https://www.mdpi.com/2072-6651/12/12/747/htm

"Overview of the Anticancer Potential of the “King of Spices” Piper nigrum and Its Main Constituent Piperine"

I just wanted to post this again separately as I think it is a good compromise for incorporating a protocol of dasatinib, quercetin, fisetin and bioperine.

I just did another protocol this week as follows.  I wanted to do both the Dasatinib + Q and the Fisetin + Q instead of doing two separate protocols.  What I ended up doing was taking 100mg of Dasatinib with 500mg of Quercetin in the morning, either before or after I had eaten.  In the evening, on an empty stomach, I took 1500mg of Fisetin and 1000mg of Quercetin all mixed in olive oil with a couple of 10mg pills of bioperine (piperene).  I did this for 3 days in a row.  (I am 69 and about 175kg)

The reason I separated them like this is that I did not want to potentiate the effect of the Dasatinib as I am somewhat leery of getting too high a dose of that, but I wanted to potentiate the Fisetin/Quercetin so that it was absorbed better. 

With this protocol the only real side effects were some headache from the Dasatinib, and some slightly loose stools on the fourth day rather than the all day diarrhea that I had experienced earlier after 2 doses of Dasatinib at 200mg and Quercetin at 1gm with bioperine...

Dan Nave hello, after some research I've found that bioperine potentiates flavanols.... Like fisetin and Q. The primary way to potentiate Dasatinibis taking it with grape fruit juice (white works best, not pink). But separately the dosing is not generally needed unless you continue to take the large dose of Dasatinib instead of half in the am and the other in the pm.  You might try just splitting it all am and pm.  The GF juice does not potentiate Q or Fisetin but it certainly does for the D!  Be careful with other meds you take as the GF juice effect lasts about 12 hours but only affects certain meds.  If you have other meds search their names with ' and Grapefruit juice' .

JGC Isn't the action of Bioperine in the intestines, rather than in the blood?