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.
This all comes from Dr. Green's site. https://senolyticstreatment.com/ at bottom of site. also, EXCLAMATIONS, and clinical trials.
12. THE NEW ANTI-AGING FORMULA
Dose and Interval
Rapamycin 3-6 mg; once a week
Dasatinib 50 mg capsules; 2 capsules a day for 3 days; once a month to 4 times a year.
Fisetin 100 mg capsules; 1500 mg once a day for 3 days; once a month to 4 times a year; taken with Dasatinib.
[Quercetin 1000 mg can be use in addition to Fisetin]
Zithromycin 250 mg tablets; 1 tab day for 6 days; once a month.
Doxycycline 50 mg capsules, 1-2 capsules a day.
Vitamin C capsules; 250-500 mg a day.
Metformin ER, 500 mg 1-4 tabs a day.
Other valuable drugs:
@Van interesting stuff. The doses by themselves seem moderate. That said together it seems a lot. I take 2mg rapamycin from Walmart once a week. Rapamycin by itself has quite an effect on me. Feel a bit like fainting sometimes, my skin itches a bit sometimes, extra thirst, shivers, brain impact during the first couple of nights after taking. Without rapa I’m in very very good physical shape. I’m concerned that without studies on monkeys first to see what this drug cocktail does just from the safety perspective put aside if it does anything for longevity, we are taking too much risk. For our safety I think we should first focus on setting up and sponsoring such studies.
Good point about statins and longevity. Statins work in just a small subset of people with specific type of ldl and then not very well. Basically if your ldl is of smaller type you need something, to reduce it. But this info can only be hypothesized from the standard lipid test. That is if your Hdl and triglycerides are good, Then your ldl is very likely to be a big fluffy type and hence nothing to worry about. even if it is above 130. That said you really need a specific test for it to know for sure. And yes in cases of very high triglycerides, high ldl and low hdl, You need to do something and sometimes all you have are statins. Further , Statins may reduce inflammation. But do they do it as well as some other drugs or even aspirin? I doubt it because they really don’t lengthen the lifespan overall in nearly all the cases. The do benefit some though.
@Van i’m not disagreeing with what you just have Just replied with. And yes the most prudent approach would be to reduce inflammation and especially so in cases like diabetes when dealing with arterial plaque formation. And yes I’m quite aware that statin beneficial effects may be due to potential inflammation reduction. And I’m not against people taking statins when prescribed by md to treat arteriosclerosis. I’m just concerned about the use of the statins for anti-aging when you don’t have any underlining conditions. Let’s say Your blood pressure is 100/60 your hdl is 80 your triglycerides are 100. You are healthy. there is no plaque in your arteries. You just happen to be 60, Is this the best course of actions for you to take statins? I say no. Will you advocate everybody to take statins for anti-aging? I say no way. There is a cost of to taking statins and your liver will pay for it. You may even live shorter if you do. Are there better alternatives? I say yes: cr,if, exercise, sauna, eat your veggies + fatty fish. Why? Because they actually can affect Together your ldl-c type which statins Can’t do. Statins are just the second gen drugs. We need the third gen ASAP. Now if you are doing senolytics you must take special ldl-c precautions but we can chat about it some other time.
Just wanted people to know. Apparently, people other than just my uncle and I have experienced a decrease in arthritis symptoms with fisetin use. The Navy is sponsoring a study to look at the effects of reducing osteoarthritis using the same dosage as the Mayo Clinic's frailty study. 20mg/kg. I am excited for this research because I have noticed such a big difference in my life, and I hope this will lead to helping more people.
@Fairy8i8 Indeed great to see formal study planned but lets' wait for the safety outcome before we start everybody on senolytics. OK? Now I don't doubt that senolytics remove senescent cells. (And yes, Fisetin appears to be safer than others.) And I have zero doubt about what excessive senescent cells do to our bodies. That said when you remove senescent cells quickly you overwhelm your body regeneration and you may cause fibrosis or worse- https://pubmed.ncbi.nlm.nih.gov/32485135/
That’s why I suspect our bodies (immune system) are less vigorous in clearing senescent cells as we age. Our body got little to replace it with, so it does a clever evolutionary trick of keeping senescent cells around by making them play some positive role too. If you remove senescent cells and don’t regenerate, this will impact quality of your life down the road. Your regenerations goes downhill after 60…..You are younger, below 40 so your regeneration is still mostly ok. The senolytic researchers are aware of regeneration limitation and are working on it to combine it with even better targeted senolytics. All that said low dose Fisetin or Quercetin on daily basis may be harmless and who knows it may help somewhat with slowing down senescence (well the research is encouraging so far).
So in summary I'm all for slowing down senescence for now but concerned about senolytics even Fisetin in mega does until we have more studies on safety and side-effects. Now if you want to experiment at your own risk with senolytics than I'm ok but please do so in organized manner. Please produce detailed records, like what you took, dosages, when, your hopefully frequent physical exams results, comprehensive blood tests, weight, blood pressure, lipids (if you read the paper i put the link to, you will know why). Those records will benefit me and others who may build on your own self experiments. And again than you for sharing good news about the study!
You are right regarding scientific aspects of such self experiments.
For me the first cycle was no fun at all. It involved some stomach pain followed by diarrhea on the first day why i extended the intake for an additional day, and feeling uncomfortable and somehow weaker in general on the next days.
The only measurable parameter i have is nightly HRV which increased about remarkable 30% since one week compared to my baseline (2 years). Unfortunately, i did not find any studies regarding the intake of senolytics and elevated HRV values. Any hints are welcome.
Just received my order for Fisetin 50 grams and Dasatinib 5 grams from China. No problems with Customs was shipped via Fedex. Fisetin was $2.50 gram including $25 Fedex. Dasatinib was $20 gram + $25 shipping. I received exactly 50 grams of Fisetin, and 5.6 grams of Dasatinib. Over paid for Fisetin, better to order online. Dasatinib and Rapamycin also are such small amounts that they can ship in an envelope and less likely to have a problem with customs. Dr. Green is now recommending to take Fisetin and Dasatinib together and you can skip or not quercetin because Fisetin works better. Green recommends 1500 mg Fisetin x 3 day x quarterly for anti ageing. I prefer to use Mayo clinic's formula of 20mg/kg. On July 01, 2020, I will take Fisetin 1700 mg x 3(with olive oil) + Dasatinib 100 mg x 3.(quarterly) The next week will take 250 mg Zithromycin x 6 days (quarterly) Will try taking Vitamin C, 500 mg with all of the above. These 3 drugs target 3 of the 4 senescent putrid cells, (aka, zombie) WIll be waiting for a treatment for the 4th. cell type.
As I understand it, Fisetin does not attack cells of any kind, it simply removes the covering or "camouflage" coating that hides senescent cells from macrophages and prevents them from being removed by normal autophagy. ... [I]t seems logical to ingest a large dose of Echinacea to stimulate our immune system about a day in advance of starting a course of Fisetin + lecithin. Reports indicate that stimulating the immune system causes it to produce more, new macrophages (or microphages in the brain) which should increase the probability of senescent cells being removed during the brief period while they're exposed.
There's a lot of misunderstanding here. I don't know where you got the idea that fisetin removes some kind of covering or camouflage from senescent cells, or that it involves the immune system; it is generally accepted that it works in a similiar way to other senolytic compounds: by inhibiting cell-survival pathways that are ramped up in senescent cells. Several such potential pathways have been identified, although none has been shown to be the one (or the main one) responsible.
Separately from senolytics, the immune system does eliminate some senescent cells, but macrophages aren't the cell type that does it: natural killer cells are. And autophagy doesn't remove cells: it removes components of cells, such as used and damaged proteins and organelles.
Has anyone seen any information that Curcumin and Fisetin counteract each other when used as a senolytic, or their different modalities of actions nullify each other? I have seen several comments to this effect, but have never seen any literature that cleared this up in my mind. Any references or thoughts would be welcome.
Does anyone have an opinion on the new Life Extension product Bio Fisetin? They claim (up to) 25 times availability, which suggests that one capsule with 8 mg of fisetin would be equivalent to 200 mg of plain fisetin. So, potentially a 4 tablet dose for 3 days might have senolytic effects???
Here's a link to the product page: https://www.lifeextension.com/vitamins-supplements/item02414/bio-fisetin
garland Thanks for your response. I am waiting on the product to arrive. I am going to take a small dose to rule out an allergic response and then try the 4 caps for 3 consecutive days. If I survive that, I'll attempt your heroic dose. :^). I will also take some of the LEF Bio Quercetin with it. If I see any obvious benefits, I'll post them here.
That sounds like a good way to start... give it time to make sure. Today I just tried my first dose of Bio-Fisetin which is many times greater potency then the regular one. I have done Fisetin at least 15 times usually about 2,300 mg... so I started with 8 of the capsules and feel it is very powerful. I feel unbelievably clear headed and full of energy and kind of 'high on life' type of feeling. But again I have done this many times and also with Dasatinib and Quercetin so go slow. You can always wait a couple of weeks and redo at a higher dose. Getting rid of old cells can be very taxing and draining and uncomfortable. But now I am sitting up straight and walking tall with a spark... but I feel this way after doing fisetin each time but this definitely feels more intense and more complete. I will know more after tomorrows when I take another dose.... and after what I feel like in a few days coming down from this session... dont ever over do it... it is not worth it.... there is always time to do another round in a few weeks...
Today I just tried my first dose of Bio-Fisetin which is many times greater potency then the regular one.
I wonder if we couldn't do this ourselves by mixing regular fisetin with, say, Guar Gum which is a galactomannan containing gum.
I have made a similar experience. Based on nothing but my own personal experience I prefer to take Fisetin on empty stomach in the morning (after having taken some black pepper or piper longum extract)
Occasionally I have used other substances a few hours (1-3h) after ingesting fisetin. I have used the senolytic activator and curcumin. And those times I have experienced what can be called side effects in the form of Headache.
Next I will order sublingual fisetin gel.
This is what brought me here, in a roundabout way. I was looking at investing, playing with stocks. I decided that I not only wanted to invest in the research but I wanted to try and improve my own health. Lots of things I had read over the years all clicked together. Here is to our health, our wealth, and our happiness.
"Unity Biotechnology, Inc. is a clinical stage biotechnology company engaged in developing therapeutics to treat ageing related diseases. The Company develops therapeutics for age-associated diseases such as arthritis, vision loss, and cognitive decline. It develops a range of Senolytic medicines that eliminate senescent cells and stop the production of Senescence Associated Secretory Phenotype. Its pipelines of products that target cellular senescence are in its clinical development stage. Its lead products candidates include senolytic molecules, UBX0101 and UBX1967, designed for local treatment for the removal of accumulated senescent cells.UBX0101 is a drug candidate developed for musculoskeletal diseases targeting osteoarthritis. It is a inhibitor of the MDM2/p53 protein interaction that eliminates senescent cells. UBX1967 is targeted at ophthalmologic diseases. It is a senolytic small molecule inhibitor of specific members of the Bcl-2 family of apoptosis regulatory proteins."
Who here has switched to the Bio Fisetin at Life Extension? Supposedly 25x the bio availability...they suggest taking around 7 caps for theoretically a 1400 mg dose. (7 caps x 8 mg x 25 bio availability). If you have switched are you noticing the same effects as mega dosing regular fisetin? Would be cheap and convenient to use the LE brand.
So I have been mixing fisetin with shea butter and applying it to myself. The big thing I notice right off is, it works as a pretty good deodorant. I work hard on the farm so this is no small thing. I did not apply it to my underarms for that reason but I will take it. Can anyone else see my logic in applying it to such a strange place? Does it also make sense to anyone else?