1079 replies to this topic

[osris]

Osris, 

 

With respect you have no grounds to reassure anyone because there isn't evidence to do so. Delayed wound healing is not something of a mere inconvenience, it can be a matter of life and death if circumstances conspire. Antibiotic failure is non-trivial, that it took Lost 16 days to get rid of what appeared a minor skin infection prompted him to stop. 

 

The very point of my mentioning the bleeding (and the dry socket which appears not to have fully healed, given it is still very heat sensitive) is because it was so unusual, highly correlative to fisetin and relates to a clotting failure - a known characteristic of senolytics. If scientifically something as weird as this is witnessed (weird in the population, and weird for me) - you don't dismiss it, you investigate. Just because an O-ring fails on a cold day and nothing too serious came of it, it should be filed under 'nothing to report'. 

 

There are three possibilities of interest: risky, little benefit; beneficial, little risk; beneficial, risky.  People tend to resolve their beliefs to one of the first two, resist the third because tension persists - but its a dangerous bias. 

 

Feeling good after 15g is not a counter-argument. I felt good too and but for a couple of unusual instances, I'd have nothing to report. But that's how it goes with high-impact low likelihood events. 

 

If you have decades in front of you there is no need to go gangbusters on senescent cells at this early stage of research, at least stay with in sensible parameters - I don't have dependents hence my risk profile is somewhat different. 

 

Anyhow, hopefully the gain of your experiment is significant and the risk low. I'll look forward to hearing of any positive developments. 

 

I’m sorry, I just can’t go along with your view that fisetin is dangerous to take. I can only go by my experience and that of hundreds of people who have taken it and had no protracted bleeding or wound healing delays. So there is really no cause to set alarm bells ringing as to fisetin’s “dangers”. 

 

I reiterate, your negative experience of it looks very much like a one-off event.

 

We can’t abandon a valuable supplement like fisetin simply because you had a bad reaction to it—assuming that reaction was connected to fisetin and not another supplement you were taking at the same time.

 

True, perhaps more research and the gathering of statistical information about protracted bleeding and wound healing delay cases needs to be done. But in the absence of that (which looks to continue being absent for many more years to come), we shouldn’t allow theoretical or hypothetical “complications” of taking fisetin to frighten us from taking it.

 

If we took that extreme cautious (if not timid) attitude towards other supplements that have a theoretical or hypothetical health risk but nevertheless benefited us, this forum would not exist.  

 

I agree with you that if you are young you shouldn’t be taking senolytics. And I am not suggesting that young people do. I'm just trying to show people who are not young that it is safe to take fisetin in particular. Other senolytics might very well be as you assume fisetin to be. I can only speak about fisetin, though.

Edited by osris, 21 January 2020 - 07:19 PM.

[bhangchai]

Any mention in research articles that I have seen of anti-platelet activity by Fisetin is seen as a net positive finding...

[ambivalent]

Osris, its not about the supplement its about the dose. Senescent cells play an important role in wound signalling - this is known - fisetin removes senescent cells, which is also known. What part of those two facts should not invite some degree of caution? In addition two people who've taken large doses (from a small sample of tail end users) have reported some concerning side-effects. We want to remove these harmful cells without compromising our ability to heal - you have just dismissed the downside and gone in at a 15g dose, reassuring everyone this is perfectly safe when you have no basis for doing so. There is no relevant sample size of data, anecdotal or otherwise, to draw on to warrant underplaying the risk of high dosing this stuff. I am certainly not negative on fisetin I have reported several benefits, far more than most, but I am clear in reaffirming the risk - something which is expected of senescent-cell removal. Getting rid of these cells is good up until a point, but going beyond it is dangerous and we are all flying blind. 

[osris]

To be clear about the dosage I took. It was not 15g. It was 1.5g a day for two days—so 3g in all.

 

Yes, 15g might very well be too high a dose to take. 

[ambivalent]

Dry socket update. I mentioned a couple of months ago suffering the afore mentioned following a tooth extraction. The clotting failure condition appears to occur in the low percent - estimates have ranged from 2-10%. In an earlier post I mentioned that after two months there was still considerable heat sensitivity, so I assumed it worryingly still hadn't healed. Thankfully that is not the case. Following a return trip, I was told that the socket had healed well but the gum beneath the adjacent tooth had contracted following the extraction, exposing the root, which led to the pain - which should improve.

[osris]

A hemostatic dressing inserted into a dry socket will eventually dissolve and meld into socket gum flesh. Dentists treat dry socket this way. You could try that. You can buy it on Ebay.

[ambivalent]

I suggest thinking before painting a post red, it is not off-topic. Dry sockets are relatively unusual and its is possible the clearance of senescent cells interfered with the clotting process. As such the present healing state 2 months on is relevant, especially as I had recently reported considerable sensitivity in that vicinity. 

 

Thanks Osris. 

[osris]

You're welcome.

 

 

 

[OP2040]

Your body clears senescent cells all the time, thus you are unlikely to accumulate decades of senescent cells. But the rate of new senescent cells increases steadily with age even as the mechanisms for removing them start to malfunction. The burden of senescent cells begins to creep up and it doesn't take many to cause a problem. They are a source of inflammation and exhibit a distinctive secretory phenotype that damages nearby cells. They thus have an outsized effect for their numbers.

 

 

With aged individuals, large numbers of cells are reaching the Hayflick limit and becoming senescent, thus senescence accelerates at that point. Cells are also becoming epigenetically old as well, thus it makes sense to eliminate them and replace them with zero age stem cells. This is something you wouldn't do every day, of course, but maybe once every few weeks for people over sixty.

 

 

I'm sure this study has been discussed here, but IMO it's one of the best studies that's been done and deserves plenty of attention.  As your post indicates. it matters a lot how senescent cells accumulate with age.  That would help guide how we treat them.  Well, now we know.

 

https://www.nature.c...467-019-13192-4

 

Basically they studied 4 hypotheses:

1. Senescent cells accumulate with age due to various forms of damage

2. Senescent cells catalyze their own production through paracrine and bystander effects

3. Senescent cell removal decreases with age due to age-related decline in immune surveillance

4. Senescent cells reduce their own removal rate via some mechanism like signaling, SASP, tissue dysfunction or immune dysfunction.

 

The study found very clearly that number 1 and 4 were the correct mechanisms.  But like any great study, it gets better. One great observation is that while Number 1 is true, the effect is linear, NOT exponential.  A second profound observation is that senescent cells very closely track the Gompertz curve.  

 

So what does this mean for implications.  Well, first of all, it adds more weight to the idea that targeting senescent cells for removal is still one of the powerful and accessible ways to intervene in aging right now.   An effective senolytic should flatten out the Gompertz curve somewhat and possibly make it much less exponential.  Truly revolutionary stuff.  But also, it tells us a lot about how we should target senescent cells.  The combination of 1/4 makes the mechanism look a lot like a simple feedback loop in which senescent cells increase at a linear rate due to damage, then those more numerous senescent cells in turn cause more damage via their own presence, thus making the process exponential  or close to it.  This makes it a truly powerful way to intervene as it breaks the cycle.  

 

What, according to this theory, will happen if we intervene to clear senescent cells?  Well, the damage may be coming from somewhere else (DNA/Environmental, etc.), so while it will lessen, there will still be a baseline of damage that will continue to drive a linear increase in senescent cells.  But the damage should in turn proceed at a much slower rate than previously.  But another weird implication arises from this.  If senescent cells are a major cause of their own production, then senescent cell clearance should become progressively easier at every successive intervention.  The first interventions should be as bold as possible, then less over time.  

 

As has been the case for a long time, the missing piece of the puzzle for senescent cells is that we can't easily measure them.  If we could, then I think this hallmark of aging would be pretty well beaten.  We would be able to intervene with increasing mathematical precision, and importantly, stop intervening when we don't need to.

[OP2040]

Does anyone thing this is too much?  F/700mg, D/100mg, Q/1000mg for 5 days?  Has anyone tried all three of these together?

[Turnbuckle]

I'm sure this study has been discussed here, but IMO it's one of the best studies that's been done and deserves plenty of attention.  As your post indicates. it matters a lot how senescent cells accumulate with age.  That would help guide how we treat them.  Well, now we know.

 

https://www.nature.c...467-019-13192-4

 

Basically they studied 4 hypotheses:

1. Senescent cells accumulate with age due to various forms of damage

2. Senescent cells catalyze their own production through paracrine and bystander effects

3. Senescent cell removal decreases with age due to age-related decline in immune surveillance

4. Senescent cells reduce their own removal rate via some mechanism like signaling, SASP, tissue dysfunction or immune dysfunction.

 

The study found very clearly that number 1 and 4 were the correct mechanisms.  But like any great study, it gets better. One great observation is that while Number 1 is true, the effect is linear, NOT exponential.  A second profound observation is that senescent cells very closely track the Gompertz curve.  

 

So what does this mean for implications.  Well, first of all, it adds more weight to the idea that targeting senescent cells for removal is still one of the powerful and accessible ways to intervene in aging right now.   An effective senolytic should flatten out the Gompertz curve somewhat and possibly make it much less exponential.  Truly revolutionary stuff.  But also, it tells us a lot about how we should target senescent cells.  The combination of 1/4 makes the mechanism look a lot like a simple feedback loop in which senescent cells increase at a linear rate due to damage, then those more numerous senescent cells in turn cause more damage via their own presence, thus making the process exponential  or close to it.  This makes it a truly powerful way to intervene as it breaks the cycle.  

 

What, according to this theory, will happen if we intervene to clear senescent cells?  Well, the damage may be coming from somewhere else (DNA/Environmental, etc.), so while it will lessen, there will still be a baseline of damage that will continue to drive a linear increase in senescent cells.  But the damage should in turn proceed at a much slower rate than previously.  But another weird implication arises from this.  If senescent cells are a major cause of their own production, then senescent cell clearance should become progressively easier at every successive intervention.  The first interventions should be as bold as possible, then less over time.  

 

As has been the case for a long time, the missing piece of the puzzle for senescent cells is that we can't easily measure them.  If we could, then I think this hallmark of aging would be pretty well beaten.  We would be able to intervene with increasing mathematical precision, and importantly, stop intervening when we don't need to.

 

 

This ignores the most important point: that senescent cells have to be replaced, but with age, stem cell niches dry up. Removing senescent cells is just half the job.

[OP2040]

This ignores the most important point: that senescent cells have to be replaced, but with age, stem cell niches dry up. Removing senescent cells is just half the job.

 

 

Yes, obviously.  But a couple things, half the job or even correcting one hallmark completely, is a very, very big deal.  Secondly, the experimental results of various studies, including even a human one, show that there are no detrimental effects of depleting these cells without a corollary replacement, and in fact by almost every measure it's good.

 

Don't get me wrong, at some point we need to follow up with the cell therapy, which IMO will be epigenetic reprogramming.  And I think those two alone will bring us to 90% problem solved.  The other hallmarks and damages I'm increasingly led to believe are almost completely dependent on these two.

[aribadabar]

Does anyone thing this is too much?  F/700mg, D/100mg, Q/1000mg for 5 days?  Has anyone tried all three of these together?

 

FWIW I have tried  a few times 100mg D +2000mg Q+ 1700mg F for 2 days every 3 months.

5 days of daily D seems excessive for senolytic purposes IMO.

[Florin]

Don't get me wrong, at some point we need to follow up with the cell therapy, which IMO will be epigenetic reprogramming.  And I think those two alone will bring us to 90% problem solved.  The other hallmarks and damages I'm increasingly led to believe are almost completely dependent on these two.

 

This is kind of OT but: it could easily turn out that this solves a lot less than 90% of the problem. Eliminating SCs and cell therapy does nothing about crosslinks in the ECM, mito mutations, junk inside cells like 7-KC, and junk outside cells like transthyretin. And there's still huge uncertainty about how well future combos of SC elimination and immunotherapy could control (nevermind completely prevent and/or cure) cancer.

[OP2040]

Ya, I've had similar discussions before and certainly reasonable people can disagree on these matters since they are hardly settled. 

 

As you can probably tell, I go by the Hallmarks of aging and not SENS.  I do notice that people usually bring up the ECM as the thing that can't be addressed with epigenetic therapy.  I would have to concede except for a single study I read.  That study basically showed that during the cellular renewal that happens with a new birth, lysosomes become highly acidic and the ecm is basically degraded then renewed.  For that reason, I'm hopeful that with epigenetic cellular renewal, there should be a concomitant renewal of ecm, though I can see why this would seem implausible at this point.  As for damages, I've never bought that every single class of macromolecular damage is some kind of really difficult problem that will require hundreds of separate cleanup regimes.  By definition, renewed cells have no problem cleaning things up, and we have many examples, including the germline, regenerative animals, negligibly senescent animals and so forth.  To take just a couple examples, does a salamanders regenerated heart tissue, or a planarians regenerated body, struggle with a dysfunctional ECM after?  Not in any literature I've read.  It can be assumed that the ECM and macromolecular damage is "taken care of" by cellular renewal.  

 

I will concede that there may be a cutoff age at which these types of damage are so pervasive that cellular renewal can't surmount them.  But even then, I'm still convinced it's 10% of the problem and a mopping up operation.

[Iporuru]

I would have to concede except for a single study I read.  That study basically showed that during the cellular renewal that happens with a new birth, lysosomes become highly acidic and the ecm is basically degraded then renewed. 

 

Can you link this study?
 

[OP2040]

Had to dig it up, but sure.

 

https://www.ncbi.nlm...23/#!po=4.05405

 

 

In C. elegans, arrested oocytes exhibit a relaxation in proteostasis, which is reversed just before fertilization when sperm signalling relieves GLD-1-mediated repression of V-ATPase synthesis. Activated lysosomes enhance oocyte proteostasis by engulfing and clearing protein aggregates, and by promoting a metabolic shift from a primed, quiescent state accompanied by elevated ROS to an active metabolic state that supports aggregate mobilization for removal. This mechanism may also underlie the sperm-dependent clearance of carbonylated proteins

 

 

Most likely the "proteostasis renewal" they are talking about is intracellular.  But the smoking gun of this study is that they found a simple switch for a complex molecular process that occurs during fertilization/oogenesis.   Lysosomes do degrade ECM through one pathway, though not sure if they are the main cause of matrix turnover or not.  The point being that we should actually expect simple triggers and mechanisms like this because they happen over and over again during embryogenesis, regenerative animals and negligibly senescent animals.  I don't see why the ECM would be some huge exception. 

 

My contention is that biology knows how to regenerate/rejuvenate and that it's a controlled process in which all manner of damages are swept away.  I highly doubt there are as many pathways for renewal as there are for entropic damage.  First of all, it would still require a high degree of parallel coordination and control, it seems implausible.

 

 

[Florin]

Ya, I've had similar discussions before and certainly reasonable people can disagree on these matters since they are hardly settled. 

 

As you can probably tell, I go by the Hallmarks of aging and not SENS.  I do notice that people usually bring up the ECM as the thing that can't be addressed with epigenetic therapy.  I would have to concede except for a single study I read.  That study basically showed that during the cellular renewal that happens with a new birth, lysosomes become highly acidic and the ecm is basically degraded then renewed.  For that reason, I'm hopeful that with epigenetic cellular renewal, there should be a concomitant renewal of ecm, though I can see why this would seem implausible at this point.  As for damages, I've never bought that every single class of macromolecular damage is some kind of really difficult problem that will require hundreds of separate cleanup regimes.  By definition, renewed cells have no problem cleaning things up, and we have many examples, including the germline, regenerative animals, negligibly senescent animals and so forth.  To take just a couple examples, does a salamanders regenerated heart tissue, or a planarians regenerated body, struggle with a dysfunctional ECM after?  Not in any literature I've read.  It can be assumed that the ECM and macromolecular damage is "taken care of" by cellular renewal.  

 

I will concede that there may be a cutoff age at which these types of damage are so pervasive that cellular renewal can't surmount them.  But even then, I'm still convinced it's 10% of the problem and a mopping up operation.

 

What does solving 90% (or even 99%) of the problem even mean? If you prevent/cure everything but ignore transthyretin aggregates, you'll probably die of heart failure shortly after hitting age 110. And increasing lysosomal acidity (even if it doesn't lead to unacceptable side effects) does nothing about junk outside of cells and might not affect all types of junk even inside cells where lysosomes operate. As for crosslinks, lysosomes are useless, because those crosslinks are located outside of cells, in the extracellular matrix (ECM). And there's no known process by which the body can safely get rid of them out in the ECM. Increasing protein turnover has been suggested as a means of eliminating the crosslinks, but that strategy runs the risk of making blood vessels leaky.

 

Supercentenarians and transthyretin amyloidosis: the next frontier of human life extension.
https://www.ncbi.nlm...pubmed/22579241

 

The Future of Aging, page 591 (ECM turnover rates)
https://books.google...epage&q&f=false

 

Extracellular glycation crosslinks: prospects for removal.
http://www.ncbi.nlm....pubmed/16706655

[OP2040]

What does solving 90% (or even 99%) of the problem even mean? If you prevent/cure everything but ignore transthyretin aggregates, you'll probably die of heart failure shortly after hitting age 110. And increasing lysosomal acidity (even if it doesn't lead to unacceptable side effects) does nothing about junk outside of cells and might not affect all types of junk even inside cells where lysosomes operate. As for crosslinks, lysosomes are useless, because those crosslinks are located outside of cells, in the extracellular matrix (ECM). And there's no known process by which the body can safely get rid of them out in the ECM. Increasing protein turnover has been suggested as a means of eliminating the crosslinks, but that strategy runs the risk of making blood vessels leaky.

 

Supercentenarians and transthyretin amyloidosis: the next frontier of human life extension.
https://www.ncbi.nlm...pubmed/22579241

 

The Future of Aging, page 591 (ECM turnover rates)
https://books.google...epage&q&f=false

 

Extracellular glycation crosslinks: prospects for removal.
http://www.ncbi.nlm....pubmed/16706655

 

 

That sounds suspiciously like a SENS view, which I don't adhere to.  I think everyone can agree that the ECM does indeed turn over, and therefore it is not a passive process of damage accumulation.  It's also common sense that cells have a large role to play in ECM turnover.  Part of that is endocytosis and part of it is MMP balance.  What, pray tell, secretes MMPs?  You got it, cells!  Where does the sensing and signaling come from that determined MMP/TIMP balance?  hmmm.  No study has been done but I'm confident that cellular rejuvenation will also at least partially rejuvenate the ECM, and vice versa.  After all, the ECM is created, then regulated, and turned over by cells!

 

The larger issue with the damage theory that SENS propounds is that there are thousands of types of damage.  It's really not indicative of how biological processes work to say that these damages just overwhelm the system at some point and that's what cause aging.  It might make sense on a superficial level, and probably what a kid would say if you asked them what causes aging.  We have counter-examples where those same thousands of types of damage are easily controlled or reversed in some animals by higher level biological processes. 

 

Not only that but the solution to the so called damages is always ablation.  We now have numerous examples of completely failed experiments for that theory.  Removing amyloid doesn't cure Alzheimer's, for example.  Removing drusen from the eye does not cure macular degeneration.  There are countless examples, else we would have cured many diseases by now.  That's because diseases, like life are processes involving both ablation and creation, not passive systems subject to entropy. 

 

If and when Aubrey cures a disease or aging by removing junk, no one will be happier than me, but I'm not holding my breath. 
 

[Florin]

That sounds suspiciously like a SENS view, which I don't adhere to.  I think everyone can agree that the ECM does indeed turn over, and therefore it is not a passive process of damage accumulation.  It's also common sense that cells have a large role to play in ECM turnover.  Part of that is endocytosis and part of it is MMP balance.  What, pray tell, secretes MMPs?  You got it, cells!  Where does the sensing and signaling come from that determined MMP/TIMP balance?  hmmm.  No study has been done but I'm confident that cellular rejuvenation will also at least partially rejuvenate the ECM, and vice versa.  After all, the ECM is created, then regulated, and turned over by cells!

Yeah, but the more you increase protein turnover above the normal rate, the higher your risk of bleeding to death.
 

The larger issue with the damage theory that SENS propounds is that there are thousands of types of damage.  It's really not indicative of how biological processes work to say that these damages just overwhelm the system at some point and that's what cause aging.  It might make sense on a superficial level, and probably what a kid would say if you asked them what causes aging.  We have counter-examples where those same thousands of types of damage are easily controlled or reversed in some animals by higher level biological processes.

I've heard about those "thousands of types of damage" before, but it always turns out that they're just dysregulated functions caused (or most likely caused) by a small set of damage or just secondary damage.
 

Not only that but the solution to the so called damages is always ablation.  We now have numerous examples of completely failed experiments for that theory.  Removing amyloid doesn't cure Alzheimer's, for example.  Removing drusen from the eye does not cure macular degeneration.  There are countless examples, else we would have cured many diseases by now.  That's because diseases, like life are processes involving both ablation and creation, not passive systems subject to entropy.

Actually, it's remove (i.e., ablation) repair (e.g., cell therapy), or render harmless (e.g., backup mito genes in the cell nucleus).

And while some diseases and conditions like AD have multiple causes, others (e.g., cancer, stroke) are dominated by a single cause (i.e., mutations and the accumulation of plaque, respectively). So, it's easy to see how heart failure after age 110 could primarily be caused by transthyretin junk.
 

If and when Aubrey cures a disease or aging by removing junk, no one will be happier than me, but I'm not holding my breath.

Well, he seems to have been right about removing SCs more than a decade before Hallmarks.

 

And to sort of get back on-topic: but we still have to be cautious about what the size of the effect of SC removal alone will be in humans.

[OP2040]

Yes, only time and more studies will tell.  I guess the really important question here is what makes mice and humans different.  We already know that what works in mice rarely works in humans.  One difference is that mice really don't live that long, even when body size is taken into account.  Another is that they have longer telomeres with a faster attrition rate.  So it seems they are well adapted to take lots of damage, the flip side of that being that they are also probably well adapted to recover much more quickly from disease states.  In contrast, humans seem to have a slower tick rate for both telomeres and epigenetic clocks.  This means we have already maxed out some of these pathways and we do indeed live a very long time. 

 

No idea what the implications of this are, just trying to start a discussion, since this seems to be the main roadblock.

[Engadin]

While fisetin bioavailabilty issue keeps unsolved when ingested, market wise, this company Gevitta, LLC develops a fisetin spray: Scepter Holdings, Inc., anticipates introduction of Fisetin infused sprays developed by Gevitta, LLC.

 

Your thoughts on this, please.

Edited by Engadin, 04 February 2020 - 06:52 PM.

[Empiricus]

Follow-up on my post #837 and subsequent reports, where I reported taking 5g of fisetin spread out over 5 days.  

 

Compared to an equivalent 5 day periods fasting, any benefits from 5g of fisetin remain unclear to me.  

Whereas low dose fisetin (200mg/day for several weeks/month) at least had a variety of immediate positive

psychological effects, I can't point to any apparent benefits form the higher dosing.  

 

Both low and high dose fisetin seemed to slow wound healing. During the period of low-dosing I had

a staph infection requiring minor operation and antibiotics, and hurt myself lifting weights in May and recovery

has been slower than from any previous such fitness-related injury I've ever had.  

 

Following the more recent high dose fisetin, I saw a setback in the recovery from the shoulder injury.  

I can't say if fisetin was to blame, but the injury became more debilitating, to the extent that I had to

stop certain exercises altogether.   The injury became more debilitating than at any time since its occurrence.

This setback occurred in December.  The injury has since been improving gradually.  

 

To summarize: the positive effects of 5 days fasting are quite striking. By contrast, I can't see that fisetin

at 5g over 5 days really does much.  At least at low doses, it put me in to a more positive state of mind.

Though even at the low dose it may have contributed to both the slow-healing and/or severity of my

staph infection and the injury sustained exercising.  

 

Another thing: As someone who is extremely sensitive to even small amounts of fisetin, I consider the

extreme lengths many people go through to try to make fisetin "more absorbable" totally unnecessary.  

I often took low doses with fish oil, but it seemed to give me a mental boost even without it. 

 

 

Edited by Empiricus, 10 February 2020 - 03:38 AM.

[Engadin]

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[SearchingForAnswers]

I took my second round, almost exactly one month later.

Dosing was: 3 days sequential at 3, 4, and 5 grams. Since the last day, I feel like utter crap. Not sure it's this, I have other health issues; but I'm hoping this is like some kind of lysis - type thing going on. Almost got chills today, tired, minor pains all over.

 

I hope I didn't overdo it.

 

 

[SearchingForAnswers]

I took my second round, almost exactly one month later.

Dosing was: 3 days sequential at 3, 4, and 5 grams. Since the last day, I feel like utter crap. Not sure it's this, I have other health issues; but I'm hoping this is like some kind of lysis - type thing going on. Almost got chills today, tired, minor pains all over.

 

I hope I didn't overdo it.

 

FYI,

 

Feeling much better today. May have just been coincidental.

 

[SearchingForAnswers]

 

I’m sorry, I just can’t go along with your view that fisetin is dangerous to take. I can only go by my experience and that of hundreds of people who have taken it and had no protracted bleeding or wound healing delays. So there is really no cause to set alarm bells ringing as to fisetin’s “dangers”. 

 

I reiterate, your negative experience of it looks very much like a one-off event.

 

We can’t abandon a valuable supplement like fisetin simply because you had a bad reaction to it—assuming that reaction was connected to fisetin and not another supplement you were taking at the same time.

 

True, perhaps more research and the gathering of statistical information about protracted bleeding and wound healing delay cases needs to be done. But in the absence of that (which looks to continue being absent for many more years to come), we shouldn’t allow theoretical or hypothetical “complications” of taking fisetin to frighten us from taking it.

 

If we took that extreme cautious (if not timid) attitude towards other supplements that have a theoretical or hypothetical health risk but nevertheless benefited us, this forum would not exist.  

 

I agree with you that if you are young you shouldn’t be taking senolytics. And I am not suggesting that young people do. I'm just trying to show people who are not young that it is safe to take fisetin in particular. Other senolytics might very well be as you assume fisetin to be. I can only speak about fisetin, though.

 

 

Just an FYI, regarding wound healing, I had a small split in the skin (in a rather personal area) heal that had not been healing. Kind of the opposite of "delayed wound healing". Does anybody really believe that fisetin kills a large enough percentage of senescent cells to actually delay wound healing? I believe I read somewhere (might be wrong) that Mayo had estimated 15% - 20%. But perhaps that was in relation to Dasatanib - Quercetin, can't remember for certain.

[HBRU]

IP6 may help both in senolitic protocols and virus infections ??

https://www.livescie...accomplice.html

[Oakman]

IP6 may help both in senolitic protocols and virus infections ??

https://www.livescie...accomplice.html

 

After reading a bit, such as...

 

https://jneuroinflam...018-1235-0#Sec1

 

I'm not sure whether knowing how to introduce the key to initiate necroptosis with IP6 is a good or bad thing. Viruses destroy cells and cause inflammation, so it seems this key may make it worse? .. or maybe make the infection over quicker? I didn't really understand enough of the study to get a good handle on its significance, or any therapies it could be applied to.

[HBRU]

After reading a bit, such as...

https://jneuroinflam...018-1235-0#Sec1

I'm not sure whether knowing how to introduce the key to initiate necroptosis with IP6 is a good or bad thing. Viruses destroy cells and cause inflammation, so it seems this key may make it worse? .. or maybe make the infection over quicker? I didn't really understand enough of the study to get a good handle on its significance, or any therapies it could be applied to.

Well infected cells have to be destroyed ASAP because there is no way to heal them. Senesent cells if you do senolitics you want to kill them: so same thing. By the way I'm preparing myself to coronavirus infection with a 5 days senolitic protocol as it seems for this virus having a lot of senesent cells around is particularly bad...
I live in Italy so the bad guy is here....