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Fisetin Study

fisetin opencures

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#31 ambivalent

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Posted 31 January 2023 - 07:43 PM

I don't agree with your definition of aging.

 

"this is what happens when we age” No, it occurs throughout our llifespan

 

“So given that senescent cells result from aging” As above, this is not true; it happens because cells age, not the host.

 

We age throughout life, not just when we are old. The point being made - let me put it you another way - senescent cells increase with time, because cell divisions increase with time - when cells stop dividing they either go senescent or to apoptosis. As time progresses - which happens to coincide with aging (which we hope to change) - we have more and more divisions and so accumulate more and more senescent cells, which are tricky to get rid of. 

 

It seems you to suppose that it is just ascredible that young people have more senescent cells than older people, than the other way round. Even if we don't know and we do know that they accumulate with age - we can look at tissues - it would be an absurd suggestion with no biological logic. What possible mechanism would explain it? That more cells have died in younger people than old? That cell apoptosis is biologically easier older than when young?

 

When stating that not all senescent cells are resist apoptosis, there is the implicit implication of another reason - autophagy, which worsens as we age. Hence the build up of damage - your reason seems to be predicated on time working in reverse. 

 

No there isn't an alternative to them not accumulating, just as I stated. The assertion is made in the presence of apoptosis - this is like contradicting that aging, the build up of damage, isn't inevitable becaue we have autophagy. It is happened to every human that has lived to be old - they all have accumulated damage - whether they have died of the damage or not and they all have had cells which perform autophagy. Senescent cells accumulate, we don't get rid of them all. When we're old we're still clearing up damage but we're accumulating more than we can cope with - hence the build up.

 

It is no longer inevitable because we have interventions and may be able to trigger apoptosis through senolytics. This is a different matter.   

 

 

Now, there is a quote directly from a paper than senescent cells accumulate with age, that the are found at increased levels found in a range of age related pathologies - you want to disagree well ok.. What you seem to be resisting is that tissue samples taken from old people aren't indicators that they accumulate with age. Why would you think that?

 

Yes of course the Biran quote is correct, limit our understanding, does not mean we dismiss our current knowledge, obviously. There are observations we can and have made which do not require us to witness in vivo.  

 

"So what we need – and seems to be lacking, which is a shame, but hopefully someone’s on it, as without it nothing else can be done – is a biometric of total senescent burden."

 

This makes no sense to me. If you have the number - then what, do you know what it means? How many do you need to get rid of? Who knows. Plenty can be done without knowing the exact amount - and I, others and a few mice can bear witness to that. 

 

If we're old we have damage, and part of that damage are senescent cells, lifestyle choices will make a difference, we may be worse or better off relative to our peers but to suggest we might not have any damage because it hasn't been measured in whole? 

 

 I can only make out that you believe you may not have any senescent cells because nebulous lifestyle choices may have irradicated them all. Well, no lifestyle choices have kept anyone alive indefinitely.

 

Nobody here has perfect information. You have to draw reasonable conclusions on the information avaialble and make a decision. Interventions on mice are good and we are all getting older. There is nothing left for me to pursue here - I am not going to a lab and take samples and provide slides. No lifestyle choice is going to make us or our cells 50 years younger.

 

 

 

 

 


Edited by ambivalent, 31 January 2023 - 07:48 PM.


#32 Zarathrustra

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Posted 14 February 2023 - 03:34 PM

Hi Ambivalent, I seem to have missed your 21st Jan response to my 20th Jan post.

 

I thought I’d addressed the points you raised already, but I will attempt to be clearer now.

 

However, I cannot follow all your points, so I’ll just stay with the fundamental points;

 

1: there  is no measure of the total amount of senescent cells a body has, none (you have yet to provide any research paper that has empirical evidence of this, rather than an assertion that it is so).

2: without such a measure, we cannot know whether

  • Increases with age – tho’ it is reasonable to think it may do; but it may not. We do not know without a measure of total senescent cell burden
  • The senescent cell burden changes with various lifestyle variables
  • If you think that there is a special class of molecules that reduces such a burden, dubbed Senolytics, then this needs to be shown empirically effecting the whole senescent burden – yet to be done. Doing it with diseased tissues (which, as far I can find, is only done by proxy of checking inflammation) does not mean it happens in healthy tissue
  • Some claimed senolytic molecules naturally occur, such as fisetin and quercetin, and so, if such are indeed senolytic, then it follows that nutrition may clear any senescent cells too.
  • If nutrition (and, for that matter, other lifestyle variables) do this, then it is possible/probable that someone adopting a healthier lifestyle later in life may well reduce their senescent cell burden. Which then would be less than when they were younger.

3: The senescent cell burden is supposed to cause ageing by increases of inflammation and reduced effectiveness of the immune system. Neither of these theories has any empirical basis. But assuming this to be so, then if inflammation reduces and/or one’s immune system improves, then this is what matters – not how some as-yet-unproven mechanism brings it about.

 

You say “What you seem to be resisting is that tissue samples taken from old people aren't indicators that they accumulate with age.” Yes, I am.

  • Taking any sample at one point in time does not tell you anything about the history of that variable
  • It is a tissue sample, not a measure of the overall senescent cell burden is it?
  • It says nothing about such people’s ageing factors, such as inflammation, hand-grip, etc, which are arguably of greater importance.

 

In sum then, the whole theory of senescent cell accumulation is, at present, an unproven theory. And Senolytics probably an illusory solution to a possible non-existing problem. Meanwhile, there are proven anti-ageing lifestyle changes that do work.

 



#33 Mind

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Posted 14 February 2023 - 05:37 PM

Since we are just repeating ourselves in this discussion, I might as well too.

 

Animal experiments with senolytics have been very positive for health and life extension. It is logical to start testing in humans - even if the theory is not completely fleshed-out. If health benefits can be had - we should pursue this course of action. It would be weird to not pursue a potential treatment that is safe and produces health benefits, just because we didn't understand the method of action 100%, or if it wasn't a true "rejuvenation" treatment. Better health, with little to no risk, could help a lot older people, while we continue to discover more solid theories of aging.

 

People knew that citrus fruit prevented scurvy long before anyone knew any of the details of how it worked. We didn't need to know anything about vitamin C, before benefiting from its effects.


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#34 Zarathrustra

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Posted 15 February 2023 - 01:05 PM

Sure, why not.

 

You say “Animal experiments with senolytics have been very positive for health and life extension”. At the risk of being boring, can you quote the research papers wherein this has been shown to be empirically true please? My own searches have failed to find them. The mice study (Whole‐body senescent cell clearance alleviates age‐related brain inflammation and cognitive impairment in mice - PMC (nih.gov)) itself notes a contradictory one (Baker), so that’s one-all. A single experiment on mice, even if one accepts its conclusions, is not one to lightly use for self-experimentation when it uses a drug, dasatinib, with known serious side-effects (include: pericardial effusion, pleural effusion, pulmonary edema, dyspnea, fluid retention, and gastrointestinal hemorrhage. Other side effects include: anasarca)

 

Some molecules called senolytics may be harmless, but Dasatinib certainly is not.

 

Given that some proposed Senolytics are contained naturally in some foods, it seems presumptuous to think existing anti-ageing lifestyle variables don’t have the same effects. So it is odd that some appear to put their research efforts into drugs/supplements rather than focussed lifestyle variables that may achieve the same or better.

 

But it goes deeper than that Senolytics, as best, has a very limited track-record and based on an unproven theory – especially regarding side-effects. My own research into fitesin and quercetin, shows fisetin corelates badly for cardiovascular status and well for body composition; quercetin badly for cardiovascular but good for cancer (I do several biomarkers for over 30 variables). Hence, I don’t supplement with either. Who knows what a double-blinded, large-scale study over decades may show up? Yet other well established anti-ageing variables (exercise, sleep, oral hygiene, etc) already have such research behind them.

 

All that said, I welcome such research, embryonic as it is, and will follow the outcomes with interest. As with my previous adaption of well-established anti-ageing lifestyle variables to my benefit (I have, overall, improved my age-related biometric results).

 

At my age, I am more careful in trying novel and unproven anti-ageing approaches, especially when the established ones seem to be paying off. I have to hope that I will live long enough to see definitive proof of any new ones in time to adopt them.

 


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#35 Mind

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Posted 15 February 2023 - 09:01 PM

Here are some studies which show some positive effects of Fisetin.

 


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#36 Zarathrustra

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Posted 16 February 2023 - 11:54 AM

Thanks Mind, but that's not at issue - as I said, I get positive results for fitesin on some of my biometrics, but negative ones on others. 

 

What matters to me is (a) how long have such trials (double-blinded?) been done? (b) have they looked for negative effects? © has the same effects been obtained by nutrition or any other lifestyle variables?


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#37 Harkijn

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Posted 16 February 2023 - 02:33 PM

Thanks Mind, but that's not at issue - as I said, I get positive results for fitesin on some of my biometrics, but negative ones on others. 

 

What matters to me is (a) how long have such trials (double-blinded?) been done? (b) have they looked for negative effects? © has the same effects been obtained by nutrition or any other lifestyle variables?

 

If these points are the ones that matter to you, why don't you just wait until they materialize? That's no problem to anyone else.


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#38 Zarathrustra

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Posted 16 February 2023 - 05:35 PM

I'm not sure I understand your comment

 

You have polled everyone else and they agree that I should not be posting my enquiries regarding senescent cell burdens and the supposed soution of enolytics? Of course, if that is so, I shall stay quiet and let my colleagues this unscientific adoption of unproven theories.


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#39 Mind

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Posted 16 February 2023 - 10:19 PM

Thanks Mind, but that's not at issue - as I said, I get positive results for fitesin on some of my biometrics, but negative ones on others. 

 

What matters to me is (a) how long have such trials (double-blinded?) been done? (b) have they looked for negative effects? © has the same effects been obtained by nutrition or any other lifestyle variables?

 

Based upon the very positive results from animal trials, fisetin is being investigated for human use. There is a Mayo clinic study that should have results soon.

 

Maybe there will be good results, maybe not, but it will advance our knowledge about senolytics, which I am sure you agree would be a good thing.


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#40 Zarathrustra

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Posted 17 February 2023 - 06:47 PM

Thanks Mind.

 

Yes, I a\gree; well conducted trials on humans is a good thing; and I will be interested in the results.

 

However, for me, the jury is alread in. It is not for me.

 

I have been trackcing my lifestyle daily now, covering 150+ supplements (amongst 400 independent variables), for over 40 years; and checking them against 100+ biometrics. From these, I know that fitesin is not for me (as I've previously said). I started doing this those many years ago as I suspected that the various recommendations for healthy living may not be true; or that at best they were based on averages and may not apply to me - as I found out.

 

I was initially impressed by the theory of accumulating cellular senescence as a major cause of ageing, along with the idea that senolytics may be a way of reducing such. Regretably, after now looking more deeply into this idea, I've found the whole area is poorly based (as I've somewhat exhaustively recounted here). There may be something in it; I await proper researsch into it. Having said that, it woujld appear at best we do not need 'senolytics', as some of those proposed are in fact naturally occuring and hence any accumulating senescent cells are already being cleared out - so one probably does not need any special senolytic supplements/drugs (the latter always being fraught with side-effects).


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#41 HBRU

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Posted 06 November 2023 - 04:42 AM

 

Some of this may be useful to you, not sure. I did this protocol a couple years ago, but it did not just include Fisetin, and so is quite different that what you have planned. Anyway, I've included the references / notes I saved from that time. 
 
The end result of taking this protocol was afterwards I felt odd/weak/weird (best I can describe and remember) for some number of days (which I did not like much), after which things went back to relative normal. But I did no testing/blood work. I have not repeated it.
 
Good luck with your trial and will be interested in the results!
======
 
"I was wondering if anyone could provide some critique of this potential study."
 
1. What fisetin dose do you think is required to produce a noticeable effect.
 
As a precursor to my Fisetin protocol, I started with a 3 day 'Senescence Activate" regimen divided into 9 doses (~1g) / 3 per day (~3g).
 
Total mixed and encapsulated:
Vitamin C 0.400mg
Watercress 0.400mg
Purple Fruit/Veg Complex 0.800mg
Betaine HCL / Pepsin 650/25 1.350mg
Ashwagandha 1.750mg
Reishi 2.000mg
Ginger 1.750mg
Zinc 0.022mg
Trans-Resveratrol - powder 0.500mg
Curcumin - powder 0.600mg
 
This was followed by a 2 day protocol - 1.25G/day Fisetin Combo (divided into three doses/day) for 2 days. The Fisetin was compounded together with Piper Longum and Quercetin as below. 
 
Total mixed and encapsulated:
Fistein pill 0.800mg
Piper Longum powder 2.000 mg
Quercetin - pill 0.500 mg
 

 

plus daily:

Vitamin D - pill 0.10mg

Black Seed Oil - 1 tsp

 
References: 
 
Inducers of Senescence, Toxic Compounds, and Senolytics: The Multiple Faces of Nrf2-Activating Phytochemicals in Cancer Adjuvant Therapy > https://www.hindawi....i/2018/4159013/
 
Natural Compounds that Remove Aging Cells > https://www.lifeexte...g-Cells/Page-01
 
 
 
 
 
T = BSO Thymoquinone  > https://www.ncbi.nlm...ubmed/24579801/
 
Resveratrol activates p53 gene
Zinc protects p53 gene against caner causing mutations
Cruciferous (w/PEITC) esp. watercress support p53
P = Phenethyl Isothiocyanate Protects against mutated p53, restores normal p53 functions
 
Enzymes for Fat Digestion https://enzymedica.c...r-fat-digestion
 
As a major mediator of the DNA damage pathway, p53 has been shown to be critical for telomeric stress-induced cellular senescence >
 
The p53 tumor suppressor protein is a latent and inactive transcription factor in unstressed cells. Following genotoxic stress or oncogene activation, this protein becomes stabilized and activated as a transcription factor, capable of inducing a transient cell cycle arrest, senescence or apoptosis.
 
Anthocyanins suppress mutated p53 cells effects
Senescence Regulation p53 > https://link.springe...1-62703-239-1_3
 

 

 

Manganese put cancer cells into senesence trough p53 too

 

Manganese superoxide dismutase induces p53-dependent senescence in colorectal cancer cells - PubMed (nih.gov)


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#42 HBRU

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Posted 06 November 2023 - 05:19 AM

Thanks Mind.

 

Yes, I a\gree; well conducted trials on humans is a good thing; and I will be interested in the results.

 

However, for me, the jury is alread in. It is not for me.

 

I have been trackcing my lifestyle daily now, covering 150+ supplements (amongst 400 independent variables), for over 40 years; and checking them against 100+ biometrics. From these, I know that fitesin is not for me (as I've previously said). I started doing this those many years ago as I suspected that the various recommendations for healthy living may not be true; or that at best they were based on averages and may not apply to me - as I found out.

 

I was initially impressed by the theory of accumulating cellular senescence as a major cause of ageing, along with the idea that senolytics may be a way of reducing such. Regretably, after now looking more deeply into this idea, I've found the whole area is poorly based (as I've somewhat exhaustively recounted here). There may be something in it; I await proper researsch into it. Having said that, it woujld appear at best we do not need 'senolytics', as some of those proposed are in fact naturally occuring and hence any accumulating senescent cells are already being cleared out - so one probably does not need any special senolytic supplements/drugs (the latter always being fraught with side-effects).

 

I think is more a matter of leading cancer cells to senesence... so making them aging and not live egoistically forever.

Cancer cells are kind similar of stem cells. This is the first goal/moment: avoid cancer / kill egoistical stem cells / transform egoistical cells in much less damaging senesent cells.

 

Second goal/moment is clear out senesent cells, but eventually and if too much.... because having some is usefull.

 

Third goal/moment is letting healthy stem cells replicate (and possibly not bad stem cells, that are the egoistical ones)... so just letting stem cells replicate no good... I have the same ideas as QuestForLife forum member.

 

Fourth goal/moment is to keep (and make) cells differentiated as with aging what happens is the loose of proper cell differentiation and we kind become a bad stem cell undifferentiated organism.... and for this I see adeguate levels of copper are necessary.... dont know why people fear copper here.


Edited by HBRU, 06 November 2023 - 05:22 AM.

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