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Fisetin: Senolytic!

fisetin senolytic

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#631 Michael

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Posted 03 June 2019 - 02:50 PM

As I understand it, fasting indues autophagy.  "Scientists have found that fasting for 12+ to 24+ hours triggers autophagy, and is thought to be one of the reasons that fasting is associated with longevity. There is a large body of research that connects fasting with improved blood sugar control, reduced inflammation, weight loss, and improved brain function; Oshumi’s research provides some of the “how” to this research. Exercise can also induce autophagy in some cells, allowing cells to start the repair and renewal process."  https://www.bluezone...-on-cell-aging/

 

That's true, but autophagy does not destroy senescent cells. I discussed this in my post.

 

Do me a favor, people: when I link something to explain a statement I make, read it before responding.


Edited by Michael, 03 June 2019 - 02:52 PM.

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#632 Gern

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Posted 06 June 2019 - 12:56 AM

Did you mix it with anything to improve bioavailability?


No, I didn’t mix it with anything. Speaking of which, it sounds like mixing it with stevia would help, but what ratio?

I also forgot to mention I got the flu like symptoms the first day. I felt flush, run-down and crappy. The second dose was much better and the rest were just fine.
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#633 ambivalent

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Posted 06 June 2019 - 03:45 PM

That's true, but autophagy does not destroy senescent cells. I discussed this in my post.

 

Do me a favor, people: when I link something to explain a statement I make, read it before responding.

 

Michael, your link went to page 15 of this thread, (Irk's post) #421 - if you (or someone) could reference the post number I'll find it.

 

It would be something of a surprise to myself and other fasters if in fact there were no clearance of senescent cells during fasting cells unless there was another explanation for the senolytic-like effects experienced during fasts.

 

I am far more experienced with fasts than senolytic protocols; however, during my significant doses of fisetin I have noticed a substantial weakening of an arthritic knee immediately after a fisetin dose, then strengthening over the days and weeks - clearance, followed by stem-cell replacement, I assume. This occurred during subsequent (months apart) doses but to a lesser extent.

 

The fasting experiences were similar, if less dramatic. Old injuries, dormant for years, become expressed during fasting, sometimes quite painfully - on occasion they can persist once a fast has broken for weeks or disappear never to return, or reappear in subsequent fasts, until the job is done - until it has re-healed. This is a very common experience. The weakening naturally feels like a cell clear-out.

 

Perhaps the most exceptional experience I noted occurred during a 5-day dry fast, which had been preceded a week earlier by one lasting 3 days was incredibly softening and smoothing of skin lasting months.

 

Whether the cell replacement, if that's occurring, is of simply old pre-senescent cells, might that serve as explanation?

 

When we consider the adage that nothing that happens in biology makes sense without considering evolution, well, we can argue similarly for the absence of a process, why doesn't senescent cell clearance occur during fasting, given the benefits?

 

My experience with Fisetin was indicative of one, a known senolytic effect - delayed wound healing: a minor nick on a wart took 5.5hours to clot. So if fasting had a senolytic effect, there would need to be boundaries. In addition the development of my arthritic knee occurred over a couple of years when I fasted substantially and indeed I've only known of fasting acting as an anti-inflammatory for those battling arthritis, not to be curative. But others may know differently.  

 

So even though the fisetin-experience was similar to those occurring during fasting it was either doing something different or reaching deeper. 

 

Anyhow, if these points are addressed in your post, which so far eludes me, then obviously there is little requirement to reiterate.

 

 

 

 

 

 

 

 

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#634 Michael

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Posted 06 June 2019 - 05:25 PM

Michael, your link went to page 15 of this thread, (Irk's post) #421 - if you (or someone) could reference the post number I'll find it.

 

It would be something of a surprise to myself and other fasters if in fact there were no clearance of senescent cells during fasting cells unless there was another explanation for the senolytic-like effects experienced during fasts.

 

First, I'm sorry for snapping at you if you tried the link and it didn't work; I'm puzzled by that, since it was working for me at the time and is still working for me now. Do you use an unusual browser?

 

Here: try manually copy-pasting the link:

 

https://www.longecit...-15#entry869671

 

Does that work?

 

Anyway, it's post #422 — just below LarryG's (not Irk's) post #421.

 

As far as your fasting experiences go: well, I too know a fair number of fasters, and I've never heard of such effects except from people doing it for the first time, and usually on the background of a very shitty diet and prediabetes. Are you being careful to maintain your electrolytes, and are you  monitoring your ketones?



#635 ambivalent

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Posted 06 June 2019 - 08:29 PM

No the link still doesn't work (with the Microsoft browser), post #422 is Daniel's for me - perhaps a date, which I'll find - that can't fail. (When I click on #421 I get ….....15#entry869795, which is probably right.)

 

I've heard modest accounts this personally from moderate fasters starting out, though they were somewhat prompted, 'it a kind of now that you mention it I have experienced this pain recurrence the last couple of weeks' since starting say starting 5:2 or etc. 

 

It was something I had anticipated occurring when I read up on 7 years ago up on the subject on some fasting site as well as perhaps on the curezone - so I wasn't blind, as it were. The first time I noticed an effect was after a week long water fast in the now (but not then afaik) arthritic knee, ligament pain surfaced I'd not experienced since cruciate ligament damage 20 years earlier. Quickly after this I moved on to dry fasting of 3 - 5 days. During this time I experienced the most painful 'repair', I suffered what appeared to be a strong reminder of a rib injury relating to a skiing accident a couple of years earlier, where the pain stayed for a couple of weeks, but would resurface during subsequent fasts and then eventually never recurred. Certainly I have read of similar accounts - I remember particularly long dry fasting (up to 9 days) and weeks long water fasting where reports of this kind occurred. xEva would serve this discussion better, she has consumed endless fasting reports. 

 

The only published research I've on injury recovery is one I posted years ago on the CR forum which I'm sure you've read. Obviously, though, its during the initial repair phase:

 

https://www.ncbi.nlm...les/PMC3119327/
 

As for my diet, when I started out it hadn't been great, but was excellent over those three or four of years. No I never got round to measuring ketones. In addition, I never experienced awful detox symptoms when starting out, though some naturally.

 

 

 

 



#636 Florin

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Posted 06 June 2019 - 11:56 PM

Here: try manually copy-pasting the link:

 

https://www.longecit...-15#entry869671

 

Does that work?

 

Anyway, it's post #422 — just below LarryG's (not Irk's) post #421.

 

As far as your fasting experiences go: well, I too know a fair number of fasters, and I've never heard of such effects except from people doing it for the first time, and usually on the background of a very shitty diet and prediabetes. Are you being careful to maintain your electrolytes, and are you  monitoring your ketones?

 

No the link still doesn't work (with the Microsoft browser), post #422 is Daniel's for me - perhaps a date, which I'll find - that can't fail. (When I click on #421 I get ….....15#entry869795, which is probably right.)

 

#419

https://www.longecit...-14#entry869671



#637 ambivalent

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Posted 07 June 2019 - 02:45 AM

That works Florin, thanks.



#638 Gern

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Posted 07 June 2019 - 08:34 PM

Amateur attempts or professional attempts, rejuvenation by a simple magic compound is unlikely. Fisetin case is simple to illustrate of this claim as this is natural compound available in small, but in non-negligible amounts in strawberries. Cosmetics industry has investigated every possible plant and extracts from them for their effects on skin. One can be certain that they looked for any type of berry on Earth and extracts from them. They have not needed to investigate fisetin per se, if there would be slightest real effect on the skin from an extract they would look in great detail what is responsible for it. They know that the sthituff like vitamin E makes skin looking better and they use it massively.

Now, skin rejuvenation is theoretically not excluded due to the existence of mechanism of partial resetting of the clock of stem cells and growing the new cells from them. But this is an entirely different ball game with tons of potential side effects looming.

. At 160ug/g the amount of Fisetin in strawberries is negligible. It would take almost 14 lbs to get a gram of fisetin. The synolytic effect of a bowl of strawberries is probably negligible.
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#639 Vastmandana

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Posted 07 June 2019 - 09:15 PM

im quiting supplements. the risk of paying so much money for no benefit or risky benefit? give me a break. i rather take something thats free. and thats why i asked if anyone knows if fasting is senolytic. how does your study answer my question? some silly rat study done in questionable way doesnt answer what i asked. in fact, im surprised there is even any positive study to fasting considering the "fasting companies" arent there to support ;)

Gaba...first, I'll agree that many folks take the "easy" road of popping pills, having been marketed to death that there's an "easy" path to longevity and good health while they are also encouraged to shovel town's of "shit" foods into their gullet's. I cant decide whether YOU are really trying to sort things out or if you're just an idiot attention seeking troll...your non stop postings about unsettled science are irritating and mostly time wasting. However, I WILL answer ur repeated question...

YES! Fasting is the best FREE way to induce atophogy, (the goal of "Senolytic" compounds) thus making it an EXTREMELY useful tool. There are sooooo many benifits to intermittent fasting...the pattern of non stop eating promoted by fucked up corporate food combines using distorted science is quite disgusting.

I have a suggestion... quit wasting your [and our] time posting here and subscribe to Siim Land's YouTube channel ( https://www.youtube....-3gEp5QF1WlM9_w) where he goes deep into fasting, low carb diets, the importance of intense exercise, the benifits of ketosis, and other things you might find useful...indeed, he's written an entire book about atophogy and ways to optimize ur life, many of which I'm SURE you'd find beneficial, IF YOU HAVE THE GUTS TO PUT OUT THE EFFORT! Call me a bit cynical, but DOING shit requires FAR MORE effort than just typing on a keypad, blathering all day

Oh, there IS one other HUGE free and VERY IMPORTANT thing you can do to improve ur health and maximize longevity... get OFF YOUR BUTT and EXERCISE! This is free, essential, and more beneficial than all the therapeutic interventions we are toying with. Even David Sinclair admits the ONLY sure thing we have thus far nailed down is exercise and diet WORKS!

I am a healthy 68 years young, log around 1000 calories of exertion per session on an eliptical 3-4 days/week and push myself in muscle strengthening sessions 2-3xs/week. My body is no longer drowning in our modern day system of sugar/carbs dietary death and uses ketones most of the time. REAL Exercise, a healthy low carb diet and intermittent fasting are wise use of time and energy. Judicious use of supplements is the cream on top of the cake (which i no longer eat...) Yes, I take a lot of promising compounds...at 68, I can't wait for definative results...but exercise due diligence in organizing my raft of longevity "assistants" and don't need a bunch of blather about it...we KNOW we're in the middle of a mystery...

Edited by Vastmandana, 07 June 2019 - 09:49 PM.

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#640 Michael

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Posted 08 June 2019 - 02:59 AM

Gaba...first, I'll agree that many folks take the "easy" road of popping pills, having been marketed to death that there's an "easy" path to longevity and good health while they are also encouraged to shovel town's of "shit" foods into their gullet's...
 
 There are sooooo many benifits to intermittent fasting...

Oh, there IS one other HUGE free and VERY IMPORTANT thing you can do to improve ur health and maximize longevity... get OFF YOUR BUTT and EXERCISE! This is free, essential, and more beneficial than all the therapeutic interventions we are toying with. Even David Sinclair admits the ONLY sure thing we have thus far nailed down is exercise and diet WORKS!

I am a healthy 68 years young, log around 1000 calories of exertion per session on an eliptical 3-4 days/week and push myself in muscle strengthening sessions 2-3xs/week. My body is no longer drowning in our modern day system of sugar/carbs dietary death and uses ketones most of the time. REAL Exercise, a healthy low carb diet and intermittent fasting are wise use of time and energy. Judicious use of supplements is the cream on top of the cake (which i no longer eat...) Yes, I take a lot of promising compounds...at 68, I can't wait for definative results...but exercise due diligence in organizing my raft of longevity "assistants" and don't need a bunch of blather about it...we KNOW we're in the middle of a mystery...

I certainly agree that people should eat well and exercise: these are well-established and low-risk interventions, and you're a Damned Fool if you don't take advantage of them before conducting an uncontrolled trial on yourself. However, regarding your first sentence, I think we should be careful not to slide into Puritanism — or perhaps the Calvinist work ethic is a closer metaphor. We must guard against the prudish and morally corrupting idea that health and longevity are things people should have to earn through meritorious effort and suffering — and conversely, when and if genuinely effective anti-aging therapies come about in pill form, we should all jump for joy and encourage our Doritos-eating, couch-parking neighbors and friends to partake, rather than sneering at "quick technological fixes" or wringing our hands over whether people will keep eating their broccoli.
 

YES! Fasting is the best FREE way to induce atophogy, (the goal of "Senolytic" compounds

 
I posted about this above, and previously: autophagy does not kill senescent cells, and here is zero evidence that any senolytic compound works through inducing it. (For those for whom that link doesn't work: try searching:
20844316a 29575469a
...in the advanced search, omitting the appended "a" in both). See this table, delineating the mechanisms of action of the great majority of known senolytic drugs:
 

gallery_727_15_20937.jpeg

"SCAP:" Senescent Cell Anti-apoptotic Pathway. From  J Am Geriatr Soc 65(10):2297-2301 PMID: 28869295

 
UNITY's proprietary molecules would also fit in this table, being variously interruptors of the MDM2-p53 interaction, and Bcl-2 inhibitors.


Edited by Michael, 08 June 2019 - 03:01 AM.

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#641 Harkijn

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Posted 09 June 2019 - 07:23 AM

I think this thread could edge a little bit closer to fisetin ;)  so I would like to draw your attention to this recent and very readable overview of (combined) natural compounds as senolytics.

Attached Files


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#642 Mind

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Posted 09 June 2019 - 11:08 PM

I certainly agree that people should eat well and exercise: these are well-established and low-risk interventions, and you're a Damned Fool if you don't take advantage of them before conducting an uncontrolled trial on yourself. However, regarding your first sentence, I think we should be careful not to slide into Puritanism — or perhaps the Calvinist work ethic is a closer metaphor. We must guard against the prudish and morally corrupting idea that health and longevity are things people should have to earn through meritorious effort and suffering — and conversely, when and if genuinely effective anti-aging therapies come about in pill form, we should all jump for joy and encourage our Doritos-eating, couch-parking neighbors and friends to partake, rather than sneering at "quick technological fixes" or wringing our hands over whether people will keep eating their broccoli.
 

 
I posted about this above, and previously: autophagy does not kill senescent cells, and here is zero evidence that any senolytic compound works through inducing it. (For those for whom that link doesn't work: try searching:
20844316a 29575469a
...in the advanced search, omitting the appended "a" in both). See this table, delineating the mechanisms of action of the great majority of known senolytic drugs:
 

gallery_727_15_20937.jpeg

"SCAP:" Senescent Cell Anti-apoptotic Pathway. From  J Am Geriatr Soc 65(10):2297-2301 PMID: 28869295

 
UNITY's proprietary molecules would also fit in this table, being variously interruptors of the MDM2-p53 interaction, and Bcl-2 inhibitors.

 

Forgive me for my ignorance on the pathways Michael, but are all the substances listed in the table senolytic (either in vivo, or in vitro) - achieving the desired goal, getting rid of senescent cells to some degree?


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#643 Michael

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Posted 09 June 2019 - 11:23 PM

Forgive me for my ignorance on the pathways Michael, but are all the substances listed in the table senolytic (either in vivo, or in vitro) - achieving the desired goal, getting rid of senescent cells to some degree?

 

"See this table, delineating the mechanisms of action of the great majority of known senolytic drugs:" ;) .


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#644 Mind

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Posted 10 June 2019 - 05:55 PM

"See this table, delineating the mechanisms of action of the great majority of known senolytic drugs:" ;) .

 

Another bad on my part....a bad question...

 

I had a tough time following the thread from "autophagy is not senolytic" and then the table.

 

So the point is that some people had thought that autophagy was senolytic, it is NOT.... and all of the compounds in the table ARE.


Edited by Mind, 10 June 2019 - 05:55 PM.

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#645 Woody42

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Posted 22 June 2019 - 03:23 PM

In the Mayo Clinic  trials was the fisetin taken in one dose or in several smaller doses during the day

and was it mixed with anything to improve it's absorption if so do we know what ?

 



#646 PerfectSeek

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Posted 13 July 2019 - 01:25 PM

Going to document my experiences with multiple 3-4 day cycles of fisetin. These were not controlled experiments so take everything as anecdote.

I’m 33 yo male, no major health issues.

I’ve cycled nuvosetin (Drs Best) at a dosage of 300mg-1g per day several times before. Each cycle lasted about 3 days. During the cycles, I would notice a slight improvement in mental acuity, and occasionally but not always, some cold like symptoms (sore throat, etc). Nothing crazy and I did typically feel slightly “better” a few days after the cycle completed. But this is subjective and not like night and day.

During the latest cycle, I switched to Rev genetics Fisetin, and increased the dose to 1.5-2.0g/day for 3 days. I did take it with meals, I tend to believe this increases absorption. It was spread into 2 doses per day.

I’m not sure why, possibly the dosage, but this latest cycle hit me “hard”. I felt very awake, stressed, motivated, and had a difficult time sleeping for these few nights. It was as if I couldn’t wind down and relax.

On the third day, I sort of hit a wall, and had extreme fatigue. I decided to skip the evening dose. Today is t+1 after the 3 day cycle and I still feel like I’ve gotten hit by a truck. Massively lower energy levels.

I’ll update if I feel amazing in a week, but the experience this time has been decidedly negative so far.

Anyways just sharing my experience

Edited by PerfectSeek, 13 July 2019 - 01:25 PM.

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#647 Oakman

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Posted 24 July 2019 - 05:57 PM

yeah. is it not possible to extract the fisetin from strawberries and sell it as supplement? i just wont get the current fisetin on the market. ill wait until we have a better source. same with resveratrol. when we have it actually extracted from grapes and not knotweed from china

 

Apparently, strawberry extract (fisetin) is available, from, of course, China. I know you don't trust them (and who would?), but you could have it analysed.

 

https://www.alibaba....etin-98%25.html



#648 Michael

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Posted 24 July 2019 - 07:21 PM

I have, as cleanly as practicable, moved the discussion of possible strawberry overdose into the nutrition Forum as being tangential at best to the subject of the thread; anyone wishing to carry on discussion of that matter, please do so there.


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#649 Dstein

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Posted 25 July 2019 - 12:43 PM

Apparently, strawberry extract (fisetin) is available, from, of course, China. I know you don't trust them (and who would?), but you could have it analysed.

 

https://www.alibaba....etin-98%25.html

 

Check out purebulk.com. Upon request, they will provide a 3d party COA.


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#650 Dstein

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Posted 17 August 2019 - 01:42 PM

A very good review on senescent cells and senolytics: Targeting normal and cancer senescent cells as a strategy of senotherapy.  [/size]http:dx.doi.org/10.1016/j.arr.2019.100941

Edited by Michael, 17 August 2019 - 03:09 PM.
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#651 Michael

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Posted 17 August 2019 - 03:11 PM

Dstein, others: again, please do not post links to sites providing back doors through paywalls: you're putting Longecity at risk of paratrooping lawyers and takedown bombardment.


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#652 Dstein

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Posted 17 August 2019 - 03:18 PM

Dstein, others: again, please do not post links to sites providing back doors through paywalls: you're putting Longecity at risk of paratrooping lawyers and takedown bombardment.

 

Is it ok to make a statement like "the article is freely available from sci-hub"?


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#653 Woody42

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Posted 03 September 2019 - 11:41 AM

I believe in the Mayo Clinic study the fisetin was mixed in    60% phosal 50  PG, 30% Peg400  and 10% ethanol.

Anyone know of a cheap source of phosal 50 PG ?


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#654 Mind

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Posted 18 September 2019 - 03:11 PM

A risk-benefiit analysis of Fisetin. From the studies so far (no human trials), benefits look to outweigh the risks.

 

https://brain.foreve...nolytic Therapy


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#655 smithx

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Posted 21 September 2019 - 08:33 AM

Mind, thanks of that link.

 

One question for you (and everyone). They say:

  • Measure baseline senescent cell load biomarkers including SA-β-gal activity, p16Ink4a expression, p21Cip1 expression, and SASP factors: IL-6, IL-8, MCP-1 when possible

Is it possible? Where can one get those tests?

 

 

A risk-benefiit analysis of Fisetin. From the studies so far (no human trials), benefits look to outweigh the risks.

 

https://brain.foreve...nolytic Therapy

 



#656 aribadabar

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Posted 21 September 2019 - 01:49 PM

Mind, thanks of that link.

 

One question for you (and everyone). They say:

  • Measure baseline senescent cell load biomarkers including SA-β-gal activity, p16Ink4a expression, p21Cip1 expression, and SASP factors: IL-6, IL-8, MCP-1 when possible

Is it possible? Where can one get those tests?

 

With the exception of IL-6 and IL-8, the rest are impossible to obtain by the general public. They are probably tested only in dedicated studies.


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#657 sedentary

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Posted 23 September 2019 - 11:44 PM

hi. one of the metformin threads that i follow led me to this place. i dont know much about fisetin except it seems to be found predominantly in strawberries  compared to any other source. and that it might in fact increase lifespan based on few animal studies. i have a question though which is more direct than just seeking various science articles and such. what about people using fisetin on this thread, what are their reports so far and how long have you guys been using this? i want to know personal experiences and not read various science articles considering its animal related. anyone on here, i assume who has been using it for a while, to report any benefit of any sort whatsoever???


Edited by sedentary, 23 September 2019 - 11:45 PM.

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#658 OP2040

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Posted 24 September 2019 - 03:50 PM

https://www.scienced...278691519306143

 

 

 

Highlights

Fisetin ameliorated lead-induced behavioral impairments in mice.

Fisetin improved synaptic dysfunction, inflammation and apoptosis in brains.

Fisetin increased autophagy and p-AMPK and SIRT1 activations in brains.

Fisetin increased SNAP-25, PSD-95, CREB and CaMKII activations in brains.

 

Not sure if anyone posted this one yet.  I'll risk it since it's publication date is December 2019 lol.  Anyway guys, I'm no longer excited by these compelling Fisetin articles as they seem to come out at a pretty fast clip, maybe monthly.

 

 

 



#659 OP2040

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Posted 24 September 2019 - 04:12 PM

 

€415 for 250 tests makes €1.66 per test. That's not expensive if enough people take part.
But as you said, a microscope is needed. It needs 200x magnification, I saw in the booklet:
 
"Observe the cells under a microscope for development of blue color (200X total magnification)."
 
Additional materials required:
 Pipettes and pipette tips
 PBS Solution
 DMSO or DMF (N-N-dimethylformamide)
 12 well plate
 
Could you do the tests for several subjects, if they send blood to you?
 
I have not yet taken fisetin, so I would be a good "before and after" test subject.

 

 

 

Microscopes are much cheaper than I thought they'd be.  I'll start with that, but the choices are a bit bewildering. Can someone tell me if this best seller from amazon hits all the marks?  It seems to have the right magnification and it's built for cellular

 

https://www.amazon.c...0NsaWNrPXRydWU=

 

This is the amazon best seller and seems to hit all the basics needed for the SA-beta-Gal  test.  Are there other conceivable tests/assays for which this type of microscope would not be enough?

 

These days I assume some software may be needed if you want to do proper analysis.  Being in the IT field for most of my life, that will be no problem, except that it's probably more expensive than the microscope itself.  Will worry about that later.



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#660 Dstein

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Posted 24 September 2019 - 08:51 PM

i want to know personal experiences and not read various science articles considering its animal related. anyone on here, i assume who has been using it for a while, to report any benefit of any sort whatsoever???

 

OK.  Here is my experience--I've done this twice, about 6 weeks apart.

 

I took ~4.2 grams (from purebulk.com) per day for 5 days.  To improve bioavailabilty, I first mixed the fisetin with MCT oil and then added liquid lecithin.

 

The first day dose each time made me sick and I generally did not feel all that great while I was taking it.  It took about two weeks to fully recover after I stopped taking the fisetin.  But after recovering my sleep greatly improved.  I am now getting the best sleep that I've had in at least 20 years.
 


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Also tagged with one or more of these keywords: fisetin, senolytic

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