$54,000
$1,097

Animal Data Shows Fisetin to be a Surprisingly Effective Senolytic

It is exciting to see animal data arrive for some of the potentially senolytic compounds that may turn out to destroy enough senescent cells in mammals to be worth using as first generation rejuvenation therapies. As a reminder, the accumulation of senescent cells is one of the causes of aging; countless cells become senescent every day in our bodies, but near all are destroyed. A tiny fraction linger to cause significant harm through the inflammatory signal molecules that they secrete. If these errant cells can be removed, then inflammatory diseases and numerous aspects of aging can be turned back to some degree. The results in mice stand head and shoulders above all of the other approaches to aging in terms of reliability and breadth of benefits.

Some senolytic compounds have been tested in animals, but a larger body of candidate senolytic drugs are presently only accompanied by cell study data. The ability to selectively destroy senescent cells in a petri dish does little more than indicate potential; there is a significant rate of failure in medical research and development for compounds with promising cell data, and any number of reasons as to why they may not work well enough in tissues or otherwise turn out to be infeasible for use in animals and humans. Fisetin was one such senolytic candidate with cell study data only, and I had not viewed it as a likely prospect. It is a flavonoid, and the one other well-known possibly senolytic flavonoid turned out not to be useful on its own - though it is helpful as a part of a combination treatment.

Given that, results from the recent animal study of fisetin noted here greatly exceed expectations, surprisingly so. Fisetin appears about as effective in mice as any of the current top senolytics, such as the chemotherapeutics dasatinib and navitoclax. Per the data in the open access paper below, dosing with fisetin destroys 25-50% of senescent cells depending on organ and method of measurement. The dose level is large in absolute terms, as one might expect for a flavonoid. For aged mice and a one-time treatment, the researchers used 100 mg/kg daily for five days. The usual approach to scale up estimated doses from mouse studies to initial human trials leads to 500 mg per day for five days for a 60kg human.

Given the wealth of new results emerging these days, it seems to me that people focused on self-experimentation, open human trials, and investigative mouse studies in this field should be moving to focus on combination therapies. Consider a combination of fisetin, dasatinib, quercetin, piperlongumine, and FOXO4-DRI - multiple different mechanisms to provoke apoptosis that are all hitting senescent cells at the same time. The goal would be to see if it is possible to engineer a significantly higher level of clearance of senescent cells than any of these senolytics can achieve on their own. This seems like a plausible goal, and may turn out to present meaningful competition to efforts such as those of Oisin Biotechnologies and other groups developing more sophisticated senolytic therapies that should have high rates of clearance.

Researchers Have Discovered How to Slow Aging

As people age, they accumulate damaged cells. When the cells get to a certain level of damage they go through an aging process of their own, called cellular senescence. The cells also release inflammatory factors that tell the immune system to clear those damaged cells. A younger person's immune system is healthy and is able to clear the damaged cells. But as people age, they aren't cleared as effectively. Thus they begin to accumulate, cause low-level inflammation and release enzymes that can degrade the tissue.

Researchers found a natural product, called fisetin, reduces the level of these damaged cells in the body. They found this by treating mice towards the end of life with this compound and see improvement in health and lifespan. "These results suggest that we can extend the period of health, termed healthspan, even towards the end of life. But there are still many questions to address, including the right dosage, for example." One question they can now answer, however, is why haven't they done this before? There were always key limitations when it came to figuring out how a drug will act on different tissues, different cells in an aging body. Researchers didn't have a way to identify if a treatment was actually attacking the particular cells that are senescent, until now.

Fisetin is a senotherapeutic that extends health and lifespan

A panel of flavonoid polyphenols was screened for senolytic activity using senescent murine and human fibroblasts, driven by oxidative and genotoxic stress, respectively. The top senotherapeutic flavonoid was tested in mice modeling a progeroid syndrome carrying a p16INK4a-luciferase reporter and aged wild-type mice to determine the effects of fisetin on senescence markers, age-related histopathology, disease markers, health span and lifespan. Human adipose tissue explants were used to determine if results translated.

Of the 10 flavonoids tested, fisetin was the most potent senolytic. Acute or intermittent treatment of progeroid and old mice with fisetin reduced senescence markers in multiple tissues, consistent with a hit-and-run senolytic mechanism. Fisetin reduced senescence in a subset of cells in murine and human adipose tissue, demonstrating cell-type specificity. Administration of fisetin to wild-type mice late in life restored tissue homeostasis, reduced age-related pathology, and extended median and maximum lifespan.

Comments

Powerful senolytic with apparently no adverse side effects, easily attainable and inexpensive, what are we waiting for? It's amazing something so simple could have such a huge impact on world life expectancy.

Posted by: Corbin at October 3rd, 2018 6:07 PM

Check clinicaltrials.gov for the Mayo human trials of fisetin. Dosage is 20 mg/kg/day for 2 consecutive days. I've already done my trial.

Posted by: Proud Daddy at October 3rd, 2018 6:14 PM

@Proud Daddy
What brand of Fisetin supplement did you use?

Posted by: Stephan at October 3rd, 2018 6:31 PM

From what I hear most of the human senolytic trials are using higher doses that you'd get by the usual method of scaling up from the relevant mouse studies. I haven't had a chance to chat to someone who knows why this is the case.

Posted by: Reason at October 3rd, 2018 6:38 PM

I am hoping to be using Senolytics within 2 years. Would anyone hazard a guess when data would show the safety and effectiveness of Fisetin? This sounds like an effective 1st gen (and low cost) Senoytic treatment. I am hoping we are talking months and not years for some definitely data results.

BTW, I looked on Amazon for what is available and cost for Fisetin.

Posted by: Robert at October 3rd, 2018 8:35 PM

@Robert
The safety is kinda already proven. It is a widely available supplement and it is considered to be a neuroprotector without proven ill side effects, if taken in moderation. Probably you will need to take a cocktail of different weak senolitics including dasatinib and navitoclax to get a detectable effect. I am not sure whether fasting for 2 weeks, can give a better effect than the weak senolitics, but that's the poors man autophagy booster that is available even now...

I waiting for OISINs mice study to finish. p53+p16 targets seem to be doing much better than the control group. My hopes are high on their approach. And i am rather skeptical about finding a strong senolytic within the existing supplements. If it was available, somebody already should have seen the remarkable effects by now.

Posted by: cuberat at October 3rd, 2018 10:43 PM

Hi there, hoping this pans out into something tangible (in humans). I think we should curb our enthusiasm (not to be pessimistic) but because mouse study results don't always translate 1:1 to human (more often than not, they don't translate at all because we have different 'specie master plans/blueprints'), with that said a 20% extension in mice might give us a 5-10 year boost in health and lifespan. I'm saying this because we already get some (though not much in general) senolytics in the food we eat or beverages drunk (red wines/red grapes, certain fruits and vegetables). This means that it may be end up being redundant (or it may synergize but I doubt it because of pathway redundancy (i.e the therapies are just emulating what these senolytics are already doing), long lived people drank (and thus consumed senolytic mimics) red wine, like centenarians (yet other centenarians did not drink once ounce of wine and ate plenty of crapfood (that kills everyone else) and Still lived to centenarian. Demonstrating, clearly, that its 'some placebo' effect there and 'mild' improvement in health - but it's genetics (epigenetics specifically, which act in concert with/to damages but superced damage as a signature you cannot just erase by removing damage/even reprogramming proved it you can't erase cell age memory) that determines if you reach a 100 or not (you inherited family genetic is also behind this, it touches the intrinsic genomic epidevelopment; which is different than the extrinsic one molded by external factors). Taking senolytics will improve external epiaging, which relates to health status (senolytics reduce SASP/p16p53/IL6/TNF, basically reduce inflammation and general stress, oxidative stress too. But, this is still something different than your DNA intrinsic epigenetic aging clock which relies on cell passaging (something uncoupled from replicative senescence/Hayflick limit and telomeres attrition; they are just independent measures of your health but the one that dictates chronological lifespan is in the methylome landscape; damages just accelerate that (as seen in Hutchison Gilford Progeria) but 'regular' 'healthy' aging is dependent on cell passaging (can be uncoupled from senescence); unlike accelerated aging (HGPS/Werner) which relies on replicative senescence acceleration). In my mind, the cell 'age memory' is what determines longevity, this signature is (so far) irreversible/permanent once written (the cell Never forgets its age and thus 'act' appropriately to its age despite being reverted to immature state ('Age 0')).

I hope they make these therapies available soon, we have been talkinb about SENS since....god knows whwen, sh*T needs to happen, we are aging and people don't give 2fcks about these therapise, they prefer botox and beautiful cremes (or even, goodness sake, surgery (f...!) of their face), face lift, and look 20 again in the mirror; who doesn't?

There is a saying (I.Newton i think) :

''Work expands as it completes itself and 'fill its time' to be made/accomplished''

which basically, means, it could take long(er), still. And we ain't gettin younger. I know we still have time and have to 'tough' it but the more time passes the more I realize we were too eager/too optimisic/too innocent, there are so many obstacles, people that don't want longevity extension, peoplpe who love to 'die' (aka fatalists) and force us 'to accept our fate and be good person with a conscience not selfish', people screaming 'overpopulation' and bs, FDA/health regulation hurdles and sh...I fear we will wait AT least another 15 years before we see ANYthing remotely 'good'. The 'news' you hear are falling on deaf tone ears and they baby steps - that scientists have been making for what? like 40 years now, baby baby babysteps one after another...- you're dead (too late), missed the boat.
It is excrutiatingly slow AF. We don't have much time (those say, hey we have 30-40 yaers ahead of us, keep on saying that, and times goes, 'you said that 10 years before??'...OK, I'm exaggerating and going on a ranty tangent a bit (sorry)). I just feel that the biogerontology domain is both its own accomplishment and its bane. Its accomplishing Great Things, yet at the same time, not much either 'in real time'; in very long time yes, not in short 'real time'. I know that thatis the 'speed' we can get and it takes huge efforts hence why so slowmo, but it's also normal for people to get fed up and just say fck it...and leave it all altogether. It,s like this Grand Project, that may never happen, when we are older, and then...sh*t..(then) what? (we're fckd/we thought all along that this grand project would save us). That is why I try to curb enthusiasm and be more real in terms of advancement with this (I am now thinking 20 years sounds about right before anything super duper big happens/ultrastagnation the name of the game (small development don't count much if they are not marketed to public and Happen tangible/be sold to humans after trials), 20 years, in 20 years I will remember I spoke about that 20 years BEFORE...and still to same point roughly).

Just a 2 cents.

Posted by: CANanonymity at October 4th, 2018 12:03 AM

@Cuberat
Regarding the idea that the beneficial effects of fisetin should have already been seen, I have been wondering about this myself.

If we assume that the effect size in humans is a ~10% gain in longevity, and then only after years of regular use starting at least in mid life - this effect might not be evident from uncontrolled anecdotes alone. And it would take a long, decently powered study to observe this in the clinic - one that as far as I can tell hasn't ever been attempted. There are a mere 5 results on clinicaltrials.gov for "fisetin," 3 of which were just started at Mayo and all of which were posted after 2016.

Now if we were talking about curcumin (183 results spanning many years) then I might be more skeptical...

Posted by: Will at October 4th, 2018 1:21 AM

@CANanonymity - a lot more impassioned than usual, I gather you feel time's running out. I'm 55 - are you older than that? I agree that humans aren't two-legged mice - we need to find much better testing methods. Now go and put some of those 2c coins in the Swear Jar :) :)

Posted by: John C. at October 4th, 2018 2:19 AM

This is a pretty cool, slam-dunk of a paper and a great 'low-hanging' fruit given fisetin's low cost and availability.

Assuming bioavailability issues can be overcome and this is translatable, fisetin alone seems to be able to reduce senescent cell load in many tissues by ~25%. It will still rise with age, even with treatment, but the burden will be less.

No doubt combinatorial therapies will be even better.

Posted by: Mark at October 4th, 2018 6:13 AM

Fisetin might be a winner.

Fisetin is found in strawberries in higher levels than other foods and a clinical trial with 60g/day freeze-dried strawberry powder reversed pre-cancerous lesions in humans.

https://www.ncbi.nlm.nih.gov/pubmed/22135048

Posted by: Lee at October 4th, 2018 6:18 AM

Re dosage and brand. I'm using Doctor's Best fisetin via Amazon. Dosage for me is 1/2 BOTTLE each day for 2 days using the Mayo clinical trial dosage. I doubt that anyone has been taking fisetin in this manner, so it isn't surprising that nobody has experienced profound benefits from regular use.

Posted by: Proud Daddy at October 4th, 2018 7:01 AM

@Will
A significant reduction in the senecent cells count should bring immediate and quite measurable health benefits. If fisetin was that good you would be witnessing major health improvements in the users. We can have several explanations what it is not the case

1. Fisetin doesn't work for humans very well 2. The bio availability is low 3. It comes with toxic sure effects. The first option basically gives no hope with this compound. The second one, requires research to improve the bioavailability (there's room for patenting medications that improve the bioavailability and that enhance the effects). It would take years for human results. The third option in a way, suggests immediate benefits. The toxicity world imply that the effects are there but not very targeted. With proper protocol the poison can become a cure. Again, they're options to patent compounds that protect non- senecent cells

And there is one more explanation that nobody noticed so far. I am not holding my breath on this. I would be glad to be proven wrong, though

@CANanonymity
Alas, what is needed is not aligned with way
What is happening. We might be on the teaching of rechuing LEV in 10-15 years. Or cold be 50 years away. And acceleration to LEV Aaron be quite uneven. People with more mean it knowledge could be 10 years ahead of the general public. For example, we (at FA and related forums) know that dasatinib should work, and the moment we have a credibile confirmation for humans, we will find a way to obtain the compound, nevermind that it costs 200$ a a gram and requires prescription. Of course, we don't know the good protocol and it is very hard to Measure the count if cenecsent cells.

Posted by: Cuberat at October 4th, 2018 8:41 AM

@Reason: from what I can tell, Human Equivalent Dose is both inexact and controversial. It's main purpose is to start human trials without killing anybody. Effective doses are often much higher than the 1/12th of mice mg/kg HED would be.

HED is based on relative surface area. The relative rate of metabolism of a drug would seem to involve a lot of other factors.

Posted by: Proud Daddy at October 4th, 2018 8:45 AM

@Reason

Do we have a theory of the damage level caused by the cenecsent cells concentration? Does it go up linearly, exponentially, less stat linearly, or does it have a more cold l complex dependency?

Is a 25% refuction enough to increase the health span? I would guess that the improvement would be more for the general population and spectacular for some isolated cases

Posted by: Cuberat at October 4th, 2018 8:48 AM

what is the right dosage for humans?

Posted by: scott emptage at October 4th, 2018 9:43 AM

@proud daddy are there any adverse effects from hugh dosages of fisetin?

Posted by: scott emptage at October 4th, 2018 10:08 AM

When purchasing some long pepper peppercorns on Amazon (after giving up on finding a good source of the root), the section titled 'Frequently Bought Together' showed a fisetin supplement; apparently people have been trying the combination.

The shipment finally arrived yesterday; I literally can't believe how good it smells. I'm hesitant to ingest it since it smells like they dunked the peppercorns in patchouli oil.

~
Strawberries deserve their reputation as a functional food; strawberry consumption is associated with reduced all cause mortality:
https://www.ncbi.nlm.nih.gov/pubmed/?term=28606222

~
I'd be happy to contribute to a crowdfunded well-designed human trial, if such a thing is possible.

Posted by: CD at October 4th, 2018 10:26 AM

@Scott. Adverse effects of high dosages are possible but unlikely. I doubt that the Mayo Clinic doctors would use them in a trial without a high degree of certainty that they're safe. I've used the half bottle dosage for two days twice now, and noticed no I'll effects.

Also, remember that maximum safe usage doses are based on continuous use, so no current guidelines would apply.

Posted by: Proud Daddy at October 4th, 2018 10:35 AM

This story is eerily reminiscent of the Phenoxodiol saga, from the Australian company Novogen, back in the late 1990s-early 2000s

Structured off another of the 6,000+ flavanoid polyphenols, it looked great in animals and cancer models, but failed to do anything meaningful in the clinic

Turned out to be a very weak chemo-sensitizer, as most of these substances end up being in humans

Probably best to save your money and eat a lot of dietary sources of these things, or which their are 000s

Posted by: DrugDev U.S. at October 4th, 2018 10:56 AM

@proud daddy when you say 2 days do you mean 2 days every week or something?

Posted by: scott emptage at October 4th, 2018 11:03 AM

@Scott. Please go to clinicaltrials.gov and get the details. So far, I've repeated the 2-day regimen once - 4 months later.

Posted by: Proud Daddy at October 4th, 2018 12:28 PM

I want to thank Proud Daddy for the info, and CD for the link. Looks promising and looking forward to the clinical study results. Also, it would be nice to hear from you Proud Daddy over the course of next couple years as well for your results as well.

Posted by: Robert at October 4th, 2018 2:26 PM

@CD. I'll be getting A1C and hsCRP in November. I'll try to remember to post the results here, but I'm 77 so...

Posted by: Proud Daddy at October 4th, 2018 3:00 PM

Over and over again, treatments that work well in mice have shown to be useless in people. We, as a species, are probably close to bumping up against intrinsic age barriers, unless we develop mutations such as the antitumor mutations found in mole rats, or the multiple copies of the p53 gene found in elephants.

We had been breeding ourselves, slowly, for longevity, by having older males have children with young females. That process has pretty much stopped, but clearly we did have a drive for longevity, whereas many other species, like mice, do not have any similar longevity driven (living longer would not benefit them reproductively), which makes increasing their life-spans "low-hanging fruit."

I take care of the very elderly, and looking at their skin, muscles, etc., probably the only thing holding them together at all are those senescent cells (and the foamy cholesterol in their arteries).

I suspect that, as mammals passed through the evolutionary bottleneck at the end of the Mesozoic, we lost crucial cellular DNA repair gene complexes. We need to examine other life forms, probably aquatic ones, to find the gene complex that repairs genes better than the existing, somewhat simple-minded ones, we have now, and find some way to integrate it into our genome.

Posted by: Benjamin Wade at October 4th, 2018 3:21 PM

@Benjamin Wade: What if we with biotech could end menopause and older women got children with younger men. Would that be the same effect?

Posted by: Norse at October 4th, 2018 3:38 PM

@Benjamin Wade: Im not sure that the effect has stopped. Today I saw a women 30 with a man 40 buying an apartment. He were so much older because that were in the age segment she could find anyone with a sufficient income. Its easier today to get jobs for women (nurses), then for men, which jobs get automated. I think the effect can speed up. There should be research on it.

Posted by: Norse at October 4th, 2018 3:42 PM

@benjamin wade "what works in mice are always useless in people?

not true, there have been things that have had just as good effect in humans like in mice. i agree with the caveat, but you can never tell for sure until a propper human trial has been conducted.

lets try and be open minded before jumping to conclusions

Posted by: scott emptage at October 4th, 2018 4:04 PM

@Norse
the funny thing is that the stronger the breeding effect is the slower the progress would be since postponing childbirth till older and older age will make the generations longer and longer. And dilate the periods. So for that effects to have a strong difference we need to wait a few generations. Say the first child is at the age of 35. 5 generations are already 150 years.... And probably there the effect would be to shift to having the first child at 40....

Posted by: cuberat at October 4th, 2018 4:09 PM

Looking at the clinical trial that was linked by CD, I see that it's phase 2, but I can't find the phase 1 trial. Has anyone seen it or know the results?

Posted by: Adam Hruby at October 4th, 2018 5:51 PM

@Benjamin Wade & Norse : Interesting idea about the age differences in relationships being a factor in life expectancy. Now that men are considered creepers if they date a women more than 5 years younger than themselves in the West, I wonder what impact this will have on life expectancy in a few generations time?

I'm speaking as more or less as a layman, but to the objections that this wont work on humans, in particular because we already likely get enough of these natural senolytics in our diets from various foods already, the following is from the Newsweek article on the study :

"The team also tested fisetin on human fat tissue in the laboratory, to see how the drug would interact with human cells, and not just mice cells. Since they were able to reduce senescent cells in the human fat tissue, the scientists think it's likely fisetin will work in humans. However, the amount of fisetin in fruits and vegetables isn't enough to have these benefits-scientists still need to work out the best dosage."

https://www.newsweek.com/fisetin-natural-fruit-vegetable-slow-aging-1151304

Posted by: The Transhumanist Runner at October 5th, 2018 12:45 AM

In a few generations I should hope we are no longer relying on the genetic crap shoot for reproduction. Longevity can be engineered in. Deciding to create a new life has always seemed to me to be more than a bit hubristic. Petulant teens do have a point - they never asked to be born. Even if a parent can guarantee a good genome, they can't guarantee that their child's life will be mostly full of joy versus suffering, if the good will outweigh the bad. In a post-singularity future, if someone wants a new person in the world, it will be possible for them to redesign themselves and they will be the only one to have to live with the outcome of their decisions. If they want another being to adore them unconditionally they can get a (possibly augmented) dog.

Posted by: CD at October 5th, 2018 10:45 AM

@Transhumanist Runner

Unfortunately, it's never just about dose, but complex pharmacokinetic and pharmacodynamic differences between species

As I said above, study the history of Phenoxodiol (one of thousands of similar compounds that have been in large scale clinical trials) to see the inherent issues of this approach

http://www.touchoncology.com/articles/phenoxodiol-chemosensitizer-midst-cancer-chemoresistance

Perhaps it may have benefit as a "seno-sensitizer"

Posted by: DrugDev U.S. at October 5th, 2018 2:25 PM

I just took 3,000 mg of Fisetin, along with 1,250 mg of Quercetin. In a few days, if I've suffered no ill effects, I plan to take 1,200 mg a day for five days. If I live, I shall write a follow up comment. I know this is foolish, dangerous and urge others to use caution.

Posted by: scottalias at October 6th, 2018 1:20 PM

The Mayo study cites 20mg/kg/day for their study. This translates into 1400 mg per day for a 70 Kg human. Is the study using Fisetin in pure form, or the version you can buy off of Amazon. How may days does one it for? A week? A month?

Someone here is using "Doctor's Best". Any others?

Any more thoughts on this?

I was planning to wait a couple of years before diving into the senolytics. But I'm now thinking I might want to give this a try.

The problem I have with the D & Q combo is that the Dasatinib is not specific enough and will kill functional cells that you don't want to kill and the Quercetin is essentially useless on its own.

Posted by: Abelard Lindsey at October 6th, 2018 7:12 PM

@scottalias
While your are taking much higher dose than what is usually recommended , it should not be life threatening, unless you have some serious kidney/liver/metabolical problems. Now there might be some harmful side effects but I am not sure that taking it orally ensures such a high bio availability. So, of you don't do the overdose now than a couple of weeks and don't have some serious problems already, you shuold
be ok... And have some more expensive pee ;)
Of course, your milage will vary...

@Abelard Lindsey
That's the catch 22. You want to kill the senecent cells, therefore you need to use something toxic. The less toxic the compound is the fewer cells it will kill. So a generally available medicine cannot be a strong senolitic without being a portion.
If the compound is highly targeted, then you limit the effect to the senecent cells. We are not there yet. Even Oisin platform is not strong enough. At least it seems to be very targeted...

So there will be some collateral damage. And here we are threading uncharted waters. We care about the senecent cells with harmful secretion. Penally killing 1 good cell for every cenecsent one is a good tradeoff. ( I don't know about the brain, though)

As for should you try it ... It is a cost versus benefit decision. If you don't have a measurable inflammation that can be blamed on cenecsent cells then I don't see much benefit. You might have some inflammation without notifying it, though.

Dasatinib has well documented side effects and the risks should be more or less clear. We don't know so we'll what will be the side effects of the d+q combo. I would err on assuming that adding quercetin is as bad as increasing the dasatinib dose. So if you are young and healthy you could easily tolerate d+q but then there will be no benefit. While I want to see human results of this combo I cannot advise you on trying it...

Posted by: Cuberat at October 6th, 2018 9:36 PM

Abelard Lindsey
I'm using the Doctors Best brand, from Amazon.

Cuberat, I am in good health, I appreciate the concern. The supplement is quite affordable. The high dose was an impulse, but I see Proud Daddy has survived essentially the same dose split over two days.

It's been nearly twelve hours and I feel fine, quite well, in fact. No negative side effects, so far, and I feel like something is happening. Don't try this at home.

Posted by: scottalias at October 7th, 2018 12:07 AM

@Benjamin Wade

" ... clearly we did have a drive for longevity, whereas many other species, like mice, do not have any similar longevity driven (living longer would not benefit them reproductively), which makes increasing their life-spans 'low-hanging fruit.'"

It would seem to me that some of it has to do with kin selection dynamics in our ancestors -- i.e., grandpas and grandmas made significant contributions to the reproductive success of their close relatives (children and grandchildren) and thus increased the frequency of their own longevity-promoting genes in the population. Not as strong an effect as we would all like (too much death by predation, accident and infection), certainly. Mice don't help their adult offspring, at all.

Posted by: cacarr at October 7th, 2018 3:26 PM

I redid the calculation. The appropriate amount of fisetin for a 70Kg person is around 700mg/day, not the 1400mg/day I cited earlier. I found the paper this blogger linked to in a previous posting about animal to human dosage calculation and have downloaded it. I am using it to calculate appropriate dosages for various senolytics as well as other stuff that may or may not remove lipofuscin. Needless to say, the next 8-12 months will be interesting for me.

Posted by: Abelard Lindsey at October 9th, 2018 8:50 PM

I took 1400mg of the Amazon "Doctor's Best" Fisetin last night, about 2 hours before bedtime. I weigh approximately 70 Kg and my age is early 60's. Administration (rather than choking down 14 pills) was to open each pill into a glass holding approximately 8 oz, then add cold water. Very little taste, not unpleasant, a little chalky.

I plan to take an additional 1400 mg tonight about the same time, then nothing more until about 3-4 months from now.

I did notice about an hour after taking it that I had a slight burning or itching on my forearms which passed quickly.

I slept well, as usual. When I first woke up this morning, I was feeling a bit hot, like I had a mild fever. That also passed quickly.

On the positive side, for quite some weeks, I've had constant inflammation/stuffiness in my nose, particularly on the right side, which is now much improved.

I do seem to have more energy this morning, but it's too soon to tell if that's real or just my imagination.

Posted by: Pete Koziar at October 10th, 2018 9:46 AM

Day 2, second 1400mg of Amazon "Doctor's Best" taken last night, about 4 hours before bedtime.

It was taken a couple of hours earlier than the night before, so I got to see more of the immediate effects. No burning or itching on my arms, just a little on my face. I did get the hot and feverish feeling again, however. I checked my temperature by mouth, and it was only up a couple of tenths of a degree. I did, however, have some shaking/trembling of my hands.

I woke up this morning after a good night's sleep, still feeling a little hot/feverish. I also had a headache, but no more shakes.

One strange effect - I could taste the fisetin again very clearly about a half hour after getting up.

By now, two hours later, it has all passed, and I'm feeling good, with a high energy level.

I plan to wait 3 months or so before taking any more of it.

Posted by: Pete Koziar at October 11th, 2018 7:06 AM

It's been six days since I took 3,000 mg of Fisetin and I've noticed a reduction the symptoms of my BPH (Benign prostatic hyperplasia). I Googled BPH and senescent cells and found a wealth of information suggesting cellular senescence is implicated as possible contributing factor to BPH, and considerable research into polyphenols in general and Fisetin in particular for treatment of BPH.

Posted by: scottalias at October 12th, 2018 1:36 PM

It's been about a week since I took 2800 mg of Fisetin across two days.

Sinus inflammation is still much reduced from what it was prior to the dosage.

Mental acuity is hard to judge, since it's affected by so many different factors (tiredness, stress, amount of sleep, etc. etc.) but I do think I'm sharper - less episodes of searching for a word, for example.

Posted by: Pete Koziar at October 17th, 2018 11:25 AM

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