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.
-
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.
-
JGC I read somewhere that tocotrienols and quercetin (both proteasome inhibitors in combo is a substitute of sorts for the dasatinib and quercetin. I have been taking these in monthly cycles using Grace tocotrienols (no tocopherol). I can't seem to find my reference for that but it is likely to be Anti-aging Firewalls or Aging Matters. I've been doing biohacking for over 20 years now and am 67. I can't say that I look any younger, but I certainly feel better at this age than at 50. No arthritis, stiffness, obesity, dark pigmentation etc. I am very interested in your experiences with fisetin. I drink many cups of black tea in a day, but add a little grass-fed milk, which may block the action of the theaflavin.
ETA (From Life Extension):Tocotrienols, the less well-known members of the vitamin E family, are emerging as the ideal senolytic nutrient. Studies show that tocotrienols have dual and complementary actions:
- In cancer cells, tocotrienols can stimulate cellular senescence, shutting down their malignant potential.6
- In healthy tissue, tocotrienols can slow aging changes, promote normal cell division and specialization, and prevent cells from reaching their damaging final aging state.10-14
Studies have shown the benefits of combining tocotrienols with quercetin, a flavonol found in many fruits and vegetables. Quercetin also has dual and complementary actions with regards to aging cells. Like tocotrienols, quercetin can induce senescence and promote cell death in numerous types of cancer cells.6,15 And, like tocotrienols, quercetin has the opposite effect in healthy cells, delaying senescence in younger cells and rejuvenating older cells to rid them of their abnormal, age-promoting function.1,6
Together, these two nutrients sweep the body clear of aging cells, while promoting natural termination of cancer cells.
-
Antonia Gauer Maybe these links can help you to find useful references about tocotrienols?
https://www.ncbi.nlm.nih.gov/pubmed/26343116
-
Staffan Olsson Yes, but there are no data supporting that tocotrienols have senolytic activity, even in cells in a dish.
-
Antonia Gauer Note that this is a conclusion that in no way follows from what they've laid out. Tocotrienols delay senescence (in cells in a dish, for reasons that have nothing to do with why cells senesce in the body), and kill cancer cells (in a dish), but they then say they "sweep the body clear of aging cells," for which they have provided zero evidence (since zero evidence existrs).
-
Staffan Olsson Thank you Staffan. The first ref is likely the one I read. It was a ref for the Life Extension article as I recall. Hard to say if it is working or not, although I always get into a "discussion" with the ferry people who want to see proof of age for free rides midweek :) A server also referred to my nephew as my father one day, which was amusing for me, but not for him (he is 58). I also do NAD+ or Niagen, with TMG for methylation, and resveratrol. But this is another discussion.
-
Iðunn Yes, a lot of evidence exists in Petri dishes. Absent of testing, all I go on is how I feel on the inside and appear on the outside.
-
Antonia Gauer Iðunn Tocotrienols show, like many other substances, potential for reducing risk for various diseases. I look forward to see what the future will hold for tocotrienols.
-
Antonia Gauer Since senescent cell accumulation is a gradual process over most of our lives, I would expect that changes caused by removing some of those cells would also be very gradual. We need a simple lab test that would provide an indication of the level of senoscent cells in living tissue. (Autopsy is not a satisfactory method for most of us.)
-
Moonlitnight Could you tell us what brands of tocotrienols and quercetin you use, what dose and how often you take it? Did you notice any particular benefits, and if so what were they and how long did it take for you to notice it?
-
Moonlitnight
Modulation of Cellular Senescence by Tocotrienols
In contrast to the pro-senescence activity displayed in cancer cells, there is substantial evidence that T3 may act as senescence delayers in normal cells by targeting ROS and molecular pathways related to the promotion of replicative senescence. Moreover, there is substantial evidence that T3 may target the pathways upstream of SASP production (mTOR and NF-kB), and it has been hypothesized that that they may eventually promote the selective death of senescent cells in particular experimental settings [40].
https://forum.age-reversal.net/t/36dhmw/fiestin-to-clear-senescent-cells
-
Juan Daw Thank you for this info - much appreciated.
-
-
Do you feel that the fiestin was more effective taken on an empty stomach? I've been on the life extension " version of the synolitic therapy, for over one month, and have noticed subtle yet profound changes. ( without the potential added benefit of taking on empty stomach) from now moving forward......
-
karl kuffner
-
karl kuffner I find," writing in this forum " to be a little challenging. , " continuing" I feel more adventurous, energetic, healthier and less body/ joint pain, and am encouraged to continue once weekly lof.senolytic. Therapy. What subjective changes have you and/or wife noticed that correlate with, " testing 8 yrs younger" wow! That's actually amazing.
-
karl kuffner
The 2018 RAADFest Age Reversal Update document advised administering D+Q on an empty stomach, so we did ours before breakfast yesterday.
The senolytic research on mice seems to favor periodic large doses of senolytic drugs rather than smaller daily doses. The idea, I think, is to hit the senescent cells hard with an infrequent big dose. Also, the worry is that daily doses of senolytics might produce cumulative side effects.
-
karl kuffner don’t know about effective but taking high doses of fisetin, quercitin or Danasitab on an empty stomach keeps me running to the toilet all day
-
Paul Beauchemin If you're taking them in oil and on an empty stomach, this can be a cause of diarrhea, as I found out the hard way 🙂 When I took senolytics in milk there were no negative side effects.
-
karl kuffner My feeling is that it is good to take Fisetin on an empty stomach so that it isn't mixed in with a mass of other food material, but that it should be taken with a bit of oil since it is not very water soluble. I always mix my F+Q with 1 Tablespoon of Olive Oil. I empty the capsules into the oil and mix it. (How hard is that? Not very, but I don't like the taste much.. ) Also add some BioPerine or black pepper at the same time.
-
-
D+Q+P Side Effects?
I do seem to notice some side effects from our D+Q+P (Dasatinib+Quercetin+Piperine) senolytic dose, taken about 24 hours ago. I had early morning stomach cramps and a mild headache, along with a mild feeling of unwellness (as if I was coming down with the flu). My temperature, however, is normal.
I take this as an indication that the D+Q+P treatment is dealing with some senescent cells in my lower digestive system and also has penetrated the blood-brain barrier. My wife has not experienced any similar symptoms.
-
Thanks for that information. Karl ps: do you, " feel" any different, being "8 yrs younger?
-
karl kuffner
Two days after D+Q+P, no cramps, no headache, no feeling of unwellness. In fact, I feel very good. Further, I do dog agility on weekends with my 5 year old Shetland Sheepdog Taliesin at the Master's level. This involves a lot of running and careful timing to keep up with the dog and to guide him over the designated jumps and contact obstacles. In the past few weeks we have done very well at Seattle-area agility trials, getting qualifying scores (Qs) in more than half of our runs on each weekend.
We will do another D+Q+P in a week (Dec. 29), and then we will have another blood test to see if there are any changes.
-
My wife and I did our second D+Q+P session yesterday (Dec. 29, 2018). This time I experienced mild diarrhea in the morning, a mild headache for most of the day and evening, and a mild feeling of unwellness during the day. The latter was similar to my experience with the first D+Q+P session. I took two 90 minute naps during the day. My wife, obviously more robust than me, reported no such symptoms. Today I feel well and energetic.
We had planned to do another blood test after these two D+Q+P sessions, but we have decided to wait a week and do a Dasatinib (200 mg) + Fisetin (2,000 mg) + Piperine (10 mg) session on January 5 before the next blood test. I'll report test results after that.
-
-
You might know about already, I did not: clinical trial to follow at Mayo. I might start with Fisetin after the first results appear, will see ...
https://clinicaltrials.gov/ct2/show/NCT03430037?cond=fisetin&cntry=US&rank=2
-
albedo
Dose is of interest: 20mg / kg (of your weight I assume. For 2 days. This is double what I did (600mg/day).
-
