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Fisetin: Senolytic!

fisetin senolytic

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#781 pamojja

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Posted Today, 11:26 AM

(and I can’t find any information or research on fisetin that even mentions potential lack of blood clotting issues)

 

See this post about agents alledged to cause serious bleeding in case-reports by NaturalStandard (2012, a bid old though): https://www.longecit...ndpost&p=614079
 


Edited by pamojja, Today, 11:27 AM.


#782 OP2040

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Posted Today, 12:45 PM

Yes, vitamin K2 probably countered any lack of blood clotting in you. I'd take it too if I were on fisetin.

 

Can you list here, for convenience, and to have it all in one place, the reasons you think fisetin is a waste of time regarding longevity? You have made some good points on this, but this thread is so long, that it would be handy to have it all in one place.

 

Presumably, you are going to take dasatinib and quercetin to simply remove senescent cells rather than for any longevity benefits. If so, why are dasatinib and quercetin, in your view, more appropriate than fisetin -- I thought the research suggested fisetin was better for senescent cell removal?

 

 

I never said Fisetin was a waste of time.  I just think it's effects are far less powerful than D+Q, possibly due to bioavailability.  It may be that it does eliminate senescent cells at a sub-clinical level, and therefore several interventions over the course of years may have the same effect as one or two D+Q interventions.  Aside from that, Fisetin seems to have many other positive affects that are not related to senescent cells.  I encourage it's use as an anti-aging intervention, the only downside being that it is fairly expensive.

 

The research does not say that Fisetin is better than D+Q for senescent cell removal.  The research says that for mice, Fisetin is the most effective senolytic among an array of natural compounds, including things like Quercetin and Curcumin.  It's senolytic effects were never compared directly to D+Q.

 

The appeal of D+Q is that it has many, many studies backing up it's very effective senolytic action, and now it has the first one showing that it works in humans as well.  Almost all the information we have on the healthspan benefits (in mice) of eliminating senescent cells, comes from studies that used the D+Q combination.  

 

I wanted Fisetin to be a simple and safe answer to the problem of senescent cells.  But I have now taken three courses of it and with no obvious effect.  Others have taken both Fisetin and D+Q and said the latter has an obvious beneficial effect and the former does not.  I strongly believe that an intervention that is actually eliminating senescent cells should show an immediate and obvious benefit to anyone over ~40.   Fisetin may still be a good choice for those looking for something more subtle and beneficial over the course of years.  Perhaps it removes 10% of senescent cells and you need 10-20 high dose sessions to achieve the same as 1 or 2 sessions of D+Q.  That is absolutely a possibility and well worth pursuing for the more patient and risk averse among us.

 

I'm not on board with worrying about blood clotting, and not convinced that K2 is what prevented it from happening to me.  This was one users unique experience, and what he described is far, far, far from a threatening situation.  Even if it was an accurate depiction and attributed to Fisetin completely, then logic dictates that it would be a temporary effect.


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#783 osris

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Posted Today, 03:17 PM

See this post about agents alledged to cause serious bleeding in case-reports by NaturalStandard (2012, a bid old though): https://www.longecit...ndpost&p=614079
 

 

That’s a very long list. But do they all really cause serious bleeding issues. I’ve been on some of these, and not found any lack of blood clogging problems.

 

Maybe fisetin is the worst of them—at least in Ambivalent's case.



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#784 ambivalent

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Posted Today, 03:17 PM

The persistent debate over whether or not fisetin is bioavailable or not is a suprise to me. As I reported back in post208 I experienced three very distinct effects which were attributable to either known properties of fisetin or senolytics (after my first dose osris). First of all my breathing improved dramatically the following day after struggling badly for months.(Fisetin inhibiting mast cells and another users experience.) I had no prior knowledge of this property.  My problematic, likely arthritic knee weakened considerably (another contributor reported the same, and it has been a consistent personal fisetin effect), then eventually strengthened above prior baseline - we know senolytic, UBX0101, can treat arthritis and trigger cartilage regrowth in mice. Several people I've known who've taken small doses of Fisetin have experienced minor detox symptoms. Then of course there was the bleeding. Once again a known property senolytics is delayed wound healing. 

 

These three effects were quite dramatic and a clear indication that fisetin was bioavailable when taken on that occasion. What is also clear is that the expression of this bioavailability would not be experienced by everyone, unless they had arthritic knees, raised levels of histamine and an untimely wart cut. As for the risk of bleeding, which is the one symptom I have some measure of doubt over as there might possibly be some other explanation* and it was not repeated, it does appear to be a transient risk, at least with me. I certainly cannot confirm whether the window of risk is repeatable, but, if it is there, it is only a window, at least personally.  My breathing has remained excellent, although this has been confounded subsequently with zinc supplementation and the knee weakness a consistent response to the fisetin dose.

 

I believe there may have been other benefits but I am far too unsure to confidently assert them such as better skin and flexibility but they definitely subjective and there is quite simply far too much noise with other protocols and most definitely not night and day effects: these were. Lost would indicate that he has had those experiences, but he has been comparatively off the scale in net-dosing. His most pronounced observation was probably the need for anti-biotics over 16 days after a skin infection - it is a chance anecdote and not necessarily attributable to fisetin, but it is an outlier of an effect.

 

As for comparing with D+Q unless they are targeting the same senescent cells, why would we expect comparable effects?

 

 

*as well as proximity to dose, a week later or so.


Edited by ambivalent, Today, 03:26 PM.


#785 osris

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Posted Today, 03:42 PM

I wanted Fisetin to be a simple and safe answer to the problem of senescent cells.  But I have now taken three courses of it and with no obvious effect.  Others have taken both Fisetin and D+Q and said the latter has an obvious beneficial effect and the former does not.  I strongly believe that an intervention that is actually eliminating senescent cells should show an immediate and obvious benefit to anyone over ~40.   

 

....

 

I'm not on board with worrying about blood clotting, and not convinced that K2 is what prevented it from happening to me.  This was one users unique experience, and what he described is far, far, far from a threatening situation.  Even if it was an accurate depiction and attributed to Fisetin completely, then logic dictates that it would be a temporary effect.

 

Not trying to call you out, but earlier in the thread, you were critical of people who expected anti-aging supplements to have observable affects on them. What has made you change your mind? Serious question, meant respectfully.

 

Regarding Ambivalent’s bleeding incident. In itself, it wasn’t serious—being only a small shaving cut. But the fact that his blood clogging ability was not working properly during this period, doesn’t rule out the possibility that he could have bled to death if the injury had been more serious, such as hitting his head on something, or merely having a tooth extracted—some tooth extraction bleedings aren’t that easy to stop under normal conditions, let alone when one is taking things like fisetin.

 

I agree that any lack of blood clotting problems would likely be only temporary, but this is no comfort if one happens to become injured to the point of significant bleeding during this temporary period. This temporary period would be enough time to bleed to death.

 

Can anyone reassure me that fisetin does not cause blood clotting problems, and that Ambivalent's experience was just down to bad luck?



#786 osris

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Posted Today, 03:50 PM

Ambivalent, I posted my last post before I saw your recent post.

 

Did you have the shaving cut after the first time you tried fisetin? If not, then fisetin can't be the cause of your excessive bleeding. 

 



#787 ambivalent

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Posted Today, 03:59 PM

Osris, no one can reassure of this: my experience was as reported, it is a known property of at least some senolytics. However, this was my first dose and it was something unexpected to my body. Also most haven't taken it with olive oil and black pepper and people have been around taking this stuff for a while at lower doses, which is obviously where you could start, without being wiped out. The tails of the distribution are undoubtedly where the risks lie, but sometimes the reward too. It is an experimental place, few of us have not been on the wrong side of our experimentation at some point. No one can tell you want you wish to hear which is that taking large doses of senolytics won't interfere with wound healing, because it seems likely that it does, nor of course that such a condition does not pose a significant risk under certain condtions. There is too of course the risk of cancer posed by senescent cell clearance, which has been discussed. 

 

 



#788 pamojja

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Posted Today, 04:07 PM

 

See this post about agents alledged to cause serious bleeding in case-reports by NaturalStandard (2012, a bid old though): https://www.longecit...ndpost&p=614079

That’s a very long list. But do they all really cause serious bleeding issues. I’ve been on some of these, and not found any lack of blood clogging problems.

 

Maybe fisetin is the worst of them—at least in Ambivalent's case.

 

In this long list I even marked 80! substances I regularly take - but never experienced increased bleeding (except with an additional baby-aspirin). As already pointed out, this list was compiled from case-reports. Even if only 1, there would be 1000s others never experience bleeding with the same substances. Or the 1 case-report was simply confounded by other things.
 



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#789 ambivalent

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Posted Today, 04:08 PM

Osris, its there in the post. Besides it would only have been a dubious timing if it occurred after a subsequent dose and I had nicked myself after prior administering of fisetin to no reduced clotting effect. Reading my initial report, I may not have added black pepper, just olive oil.



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