Fisetin to Clear Senescent Cells
Following studies with mice that showed significant senolytic clearance of senescent cells following large doses of the readily available flavenoid supplement Fisetin, my wife and I (ages 79 and 84) decided to try it. We have just completed two sets of massive Fisetin doses.
We had Life Extension blood-work done in October before the start, and we will have more again next week to observe any changes. The first set of Fisetin doses was on October 22-25 with 800 mg/day for three days followed by 600 mg on the fourth day, for a total of 4 g. I didn't notice much in the way of effects. Perhaps some reduction of small aches and pains and some increase in energy and mental acuity.
For the second set of doses done November 22-26, since we experienced no negative side effects in the first set we decided to increase the dosage a bit and to add 10 mg of BioPerine, a supplement that is reputed to magnify the effects and potency of flavenoids. For five days starting on Thanksgiving we took 500 mg of Fisetin and 10 mg of BioPerine twice per day, for a total of 5 g of Fisetin.
This time. I did experience one negative side effect. A few months ago, about 2 AM in the morning I awoke from a deep sleep and experienced a severe episode of vertigo. I turned over in bed, and the the whole room seemed to tilt. Suddenly, I didn't know which way was up. I staggered to the bathroom and vomited. The symptoms tapered off and disappeared in a few days, but it was a very distributing experience.
On the 2nd day of our 2nd Fisetin series, I experience a recurrence of that vertigo in the middle of the night, not as bad as my initial experience but still rather disturbing. I tolerated this mild vertigo and continued the treatment. My wife had no similar symptoms, and after my last dose I experienced no further vertigo symptoms.
On the positive side, following the second set of dosages I did feel very well, and very sharp and alert. This past weekend I ran my Shetland Sheepdog Taliesin in an AKC Canine Agility Trial in Mt. Vernon, WA, and we did very well, qualifying in 7 runs out of 15 and getting various colored placement ribbons. I was feeling quite sharp, and I even invented a new dog-handling technique that fixed an ongoing problem we were having.
Next week we will do the blood-work again, and I'll report any changes.
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Thank you for the info. My understanding is the Fisetin should be taken with quercetin?
I have been taking only 100mg Fisetin + 500mg quercitin daily for about 2 weeks. Can't say I have noticed any changes. Except, I did have a short duration vagus nerve zinger that included a hot flash, dizziness, nausea, near faint, and SURPRISE! Lasted only 30 seconds or so but scared the heck out of me. It occurred on the 3rd day of my 5 day fast.
Would like to read more on dosage, duration, and results from others?
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nealfg
It's Dasatinib that is supposed to be taken with Quercetin, not, to my knowledge, Fisetin. The mouse studies involved large doses of Fisetin administered alone. However, it has been pointed out that taking a small amount (10 mg) of BioPerine along with Fisetin tends to magnify the effect, since Ficetinis a flavenoid. Therefore, in our last session my wife and I took 10 rounds of 500 mg of Fisetin with 10 mg of BioPerine over five days. Note that the mouse study indicates that the most effective clearance of senescent cells is accomplished with a few massive doses of Fisetin, not with smaller amounts taken every day.
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JGC I don't think there's any evidence that piperine/BioPerine enhances absorption of flavonoids generally — just curcumin. Or do you know of any? And the mechanism isn't really understood, so it's hard to make strong predictions.
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Iðunn
I refer you to https://www.isotrope.com/bioperine/ . It says that: "P-glycoprotein is a protein the body uses to break down exogenous compounds found in the body. This protein inhibits the action of many medications, and also regulates the degree to which certain nutrients are absorbed by the body. This protein actively controls the permeability of the blood-brain barrier, which directly impacts the overall effects seen by many compounds such as curcumin—the active compound found in Turmeric. Piperine inhibits the action of this protein."
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Dan Nave BobM nealfg deahello again; Dan your wisdom and response to my questions, is very useful. after 3 consecutive days of aggressive fesitin (? Spelling) and quercetin and black tea ( help w assimilation) I've been experiencing high energy, more and then much less arthritis discomfort some euphoria, I've discontinued weekly," le senolytic activator" and will do another intense fisetin, quercetin, ( probably black pepper) and hot black tea in 30 days from now and will report on my, "experiences" thankyou all and thankyou Dan.
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nealfg
I have read the Quercetin combination with Fisetin and I take that as well. But I'm afraid 100mg is no where near enough for humans. I have taken 800mg 1st day, 800mg 2nd and 1000 mg the 3rd. I felt fine and had no side effects. I would not take anything less then 800mg because I have recently read even those doses now seem inadequate. There was one article I read that a man took 3 grams, I believe for 3 days, he was going on and on on how incredible he felt. Though I am just now trying to find the article again to verify everything. 1 to 3 month waiting period in between doses seems to be the norm. I did read once 1 year in between doses but that seems excessive. Good luck.
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Greg
*Correction* not 1 to 3 months in between doses, but 1 to 3 months after the 3 doses.
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karl kuffner I've only just seen this post but the mention of black tea is interesting. As I mention elsewhere I took 500mg of fisetin but after drinking a large cup of black & green tea with cinnamon and lemon I had a powerful sensation. Guess black tea is indeed a useful thing to have with fisetin.
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Bloodwork Results of Two Fisetin Sessions
As I stated in my first post on this topic, in the past two months my wife and I have taken two massive doses of Fisetin in an effort to clear our senescent cells. We did bloodwork arranged by Life Extension on October 22 before the first session and again on December 17 after the second session. Our goal was to determine if the Fisetin sessions had a measurable effect on our fitness, as measured by the bloodwork results. We analyzed our result values in three ways: (1) using the Aging AI website, (2) using the Young.AI website, and (3) using a calculation of Levine Phenotypic Age done with a spreadsheet that I have posted elsewhere on this site. I note that the Levine age is always close to the calendar age because the latter is one of its most important input factors. The table below summarizes the results:
Interestingly, following the Fisetin sessions my Aging AI age dropped by 8 years and my Young.AI age dropped by 3 years, but my Levine Phenotypic Age actually increased by 3 years. I think that this is because at the time of the second bloodwork I had a big bruise on my left leg from a collision with a chair in the dark a few days earlier. The inflammation from this bruise probably somewhat increased my c-reactive protein, my white blood cell count, and the blood geometry factors, all of which will increase the Levine age.
Therefore, my wife's numbers are probably more relevant. Her aging AI age dropped by 5 years, her Young.AI age dropped by 11 years, and her Levine age dropped by 1.4 years. My conclusion that the Fisetin sessions did have an observable (but not large) effect on our overall fitness, as reflected by the bloodwork.
Soon we will undertake two similar sessions with D+Q, and we will report any bloodwork changes after those.
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JGC This is awesome data, JGC! Thank you!
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JGC
I notice that JGC's October testing:DNAm Age 8 years lower than Calendar Age
Aging.Ai 30 years lower than Calendar Age
I have also recently done similar testing. I am now 69
My DNAm Age: 61 (I.e. 8 years lower)
My Aging.AI age: 39 (I.e. 30 years lower)
This makes me feel good. But the question is:
How can someone trust these numbers? If there were a few years diference between DNAm Age and Aging.AI age , the numbers might be meaningful. But with such huge differences, I am not sure what to make of them. So what is my biologcal age: 61 or 39?
I am very confused...
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Zisos Katsiapis
It is confusing. Let me see if I can make it clearer.
Aging.AI takes bloodwork vs. calendar age data from as many people as possible, does a linear fit, and uses this to predict age from bloodwork data in a particular case.
The DNAm age is based on the work of Levine, et al. They first correlate Steve Hovath's DNA methylation analysis data with calendar age, which turns out to be very predictive. Then they do a secondary correlation of bloodwork data with DNA methylation age, and use this to predict DNAm age from bloodwork. Their fit uses calendar age as one of the fit parameters (cheating?) along with the bloodwork values, so it's not surprising that their prediction does not deviate too much from actual calendar age. In the upper age range, the DNA methylation fit over-predicts age, so my spreadsheet makes a correction for this.
Why do the two age predictions differ so much? Because they are predicting different things, arrived at by different methods. All one can say is that it's better to have an Aging.AI or DNAm age that is lower than your calendar age, rather than higher. Note that DNAm is strongly dependent on a factor that indicates the variation in geometry among blood cells, while Aging.AI does not even use this factor.
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JGC Do you have updated test results you could share?
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Joe smith
I have posted here all the test results and calculated bio-ages (see above) that we have. For our last few sessions (done in NY last Summer and during the COVID-19 lock-down), it has not been convenient to do before-and-after bloodwork.
Further, from Steve Horvath's papers and videos, a person's senescent cells have about the same age-related DNA methylation pattern as the more healthy non-senescent cells, so doing a senolytic session to clear senescent cells would not be expected to change the DNAm age very much.
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JGC Thanks - which specific blood tests did you do? I signed up at Young.ai but it doesn't provide any guidance. It just says "upload blood tests".
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Aneil
In the blood lab tests we did, I wanted to provide inputs for my Levine PhenoAge spreadsheet calculation, so we used Life Extension's Complete Blood Count (CBC) / Chemistry / Lipids Panel Blood Test ($26.25), and their C-Reactive Protein (CRP), Cardiac Blood Test ($31.50). These blood tests provide the needed input values. You sign up for the tests online, and they refer you to a LabCorp center where the blood draw and analysis is done.
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JGC Thank you so much for the reply! I will give that a try.
I'd also like to find a direct measure of senescent cells. Levine is a bit indirect and might be affected by other issues (like an active wound). I know beta-galactosidase is one possibility, but I can't find a consumer lab that will do it. The value is we could share observations on which regime for sure was decreasing senescent cell abundance. -
Aneil
You have identified a real problem for those of us doing senolytic self-experiments, i.e., that there is not presently a good way of measuring the senolytic cell population before/after the treatment. The main use of the beta-galactosidase technique is to take a tissue biopsy, stain the beta-galactosidase (which turns blue), and count the fraction of blue senescent cells, as viewed in a microscope. That's usually done in a autopsy, which does not work very well for us self-experimenters.
The group of Judy Campisi at the Buck Institute has recently found that the molecule dihomo-15d-PGJ2 is uniquely released into the bloodstream when senescent cells are destroyed. In principle, that's just what is needed, except that no commercial firm offers to determine the amount of dihomo-15d-PGJ2 in a blood or urine sample. In principle, it could be done with mass-spec or ELISA, but no such test is out there yet.
This represents a commercial opportunity for some enterprising bio-lab operator (HINT, HINT, HINT)!
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JGC Ah, I see β-gal is stuck in the lysosomes of senescent cells. Thank you for the link to dihomo-15d-PGJ2. I will ask lab friends about it and post here if I learn anything useful. Thank you so much for your responses. https://www.nature.com/articles/s41422-020-0314-9
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JGC said:
...The table below summarizes the results: ..Thank you for sharing your results and also look forward to the D+Q tests!
In my case I have noticed large variations in the aging.ai results in time (~10 years) and always wondered how I can disentangle the effect from the error. v1.0 and v3.0 have also resp. an intrinsic MAE of 5.5 and 5.9 years. To understand a bit more I did try an ANOVA test which might show a little effect (only with v1.0) in lowering the aging.ai in recent years and I (would like to :-)) associate this to a regular use of metformin. Coincidence or not, I am also looking at senolytics and might try the new LEF formulation.
Good luck for your tests!
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Fisetin vs. D+Q
My wife and I have been starting our new senolytic doses on the 22nd of the month. In October and November, we took large doses of Fisetin, as reported above.
Today at 10 AM on empty stomachs, we took 200 mg of Dasatinib, 2,400 mg of Quercetin, and 10 mg of BioPerine. I'll report any side effects that we observe.
We plan to repeat this in a week, on the 29th. After that, we'll do bloodwork yet again and report any changes.
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JGC
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JGC Have you ever try the Senolytic activator by Life extension? I am into this forum trying to find answer because I got some side effect with my first two pills.
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LISBETH Prieto
I have not tried LifeExtension's Senolytic Activator. Its main senolytic ingredient is the flavenoid Quercetin. I have taken Quercetin along with Dasatinib and Bioperine (a pepper-derived supplement that greatly extends the half-life of flavenoids in the bloodstream).
The research paper that first tested and suggested Quercetin as a senolytic drug showed that (a) it tends to act on senolytic cells in the lining of blood vessels, and (b) it is far more effective when combined with the expensive anti-cancer drug Dasatinib, which goes after senolytic fat cells. The D+Q combination is a highly regarded senolytic.
LifeExtension cannot sell a D+Q pill because Dasatinib is a prescription-only drug and is prohibitively expensive ($2K for 4 pills). Therefore, they do what they presumably consider the next best thing by adding Theaflavins fron black tea as a Dasatinib substitute. However, there is no research of which I am aware indicating that Theaflavins are an effective substitute for Dasatinib.
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LISBETH Prieto
Correction: "senescent cells", not "senolytic cells".
JGC
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