1079 replies to this topic

[TaiChiKid]

I wonder about the merits of taking any senolytic continuously.  A lot of malignant cancers end out escaping elimination with the old strategy of chemo:  wipe out the malignant cells completely.  In some cancers like prostate, the cells which survive the bombardment are the ones which are resistant to the senolytic.  Those cells then multiply, and you die...  Whereas, taking a senolytic once every few years or so sweeps out the senescent cells as well as the malignant ones.  They now use a new therapy technique for the malignant cancers such as late stage prostate called 'adaptive therapy' which allows a stasis of malignant cells to survive.  They are having success with that protocol, and it costs a lot less.

Edited by TaiChiKid, 07 April 2019 - 09:47 PM.

[Woody42]

Back to that 60% phosal 50, 30% Peg400  :10% ethanol  that may have been used in the Mayo

clinic studies. Is there any idea how much of this mix would have been used per gram of Fisetin. 

[Engadin]

Hi, just for informative purposes, not a pro-sales move at all. Got it on my facebook minutes ago. Interesting chance for a buy group: 

 

 

A Minimum Of 8 Bottles To Get 50% Off. Up to this Wednesday night. Any way, always be aware of this sort of ads looking for your impulsive purchasing by means of shortening the acquisition term.

 

Link: https://mailchi.mp/r...urcumin-1395249

 

BTW, not sure this product to be as bioavailable as advertised, but those of you in the know may overcome it.

Edited by Engadin, 09 April 2019 - 12:03 PM.

[Oakman]

That's for sure a lot of fisetin per cap and per bottle, and cheap at that (8 bottle) price as well!  Another well known brand I remember was ~$10 for 30 caps of 100 mgs.

[pinballwizard]

Oakman, or Anyone, 

 

Have we found a combination of senolytics?  Something besides Dasatinib and Quercetin?  maybe dasatinib, fisetin, quercetin, piperlongumine, combined?

 

Thanks!

 

Tom  

 

 

To expand on my own question and suggested dosing, based on the article below, perhaps a 5 day regimen would be better (safer, more effective) than a higher dose 2 day one, and also combined with quercetin and piperlongumine, both of which are readily available. I'm still gauging what I will eventually try, but this is all good information.

 

"Given that, results from the recent animal study of fisetin noted here greatly exceed expectations, surprisingly so. Fisetin appears about as effective in mice as any of the current top senolytics, such as the chemotherapeutics dasatinib and navitoclax. Per the data in the open access paper below, dosing with fisetin destroys 25-50% of senescent cells depending on organ and method of measurement. The dose level is large in absolute terms, as one might expect for a flavonoid. For aged mice and a one-time treatment, the researchers used 100 mg/kg daily for five days. The usual approach to scale up estimated doses from mouse studies to initial human trials leads to 500 mg per day for five days for a 60 kg human.

 

Given the wealth of new results emerging these days, it seems to me that people focused on self-experimentation, open human trials, and investigative mouse studies in this field should be moving to focus on combination therapies. Consider a combination of fisetin, dasatinib, quercetin, piperlongumine, and FOXO4-DRI- multiple different mechanisms to provoke apoptosis that are all hitting senescent cells at the same time. The goal would be to see if it is possible to engineer a significantly higher level of clearance of senescent cells than any of these senolytics can achieve on their own. This seems like a plausible goal, and may turn out to present meaningful competition to efforts such as those of Oisin Biotechnologies and other groups developing more sophisticated senolytic therapies that should have high rates of clearance."

 

https://www.fightagi...tive-senolytic/

 

[Oakman]

Oakman, or Anyone, 

 

Have we found a combination of senolytics?  Something besides Dasatinib and Quercetin?  maybe dasatinib, fisetin, quercetin, piperlongumine, combined?

 

Thanks!

 

Tom  

 

I use a combination, last time is mentioned in this post.

[Woody42]

I spotted one company Life Extension  pushing a "senolytic activator " 

The only active ingredients being Bio quercetin and theaflavin  Anyone

else heard about this combination.   

[GABAergic]

what i would like to know is, in case of fisetin, it works as coloring agent in fruits like strawberries. how does fisetin benefit those plants as coloring agent and why do you people think that some coloring agent can actually have a positive impact on humans? that is, there is not a single study done on humans to show benefit. i know there are lot of studies claiming its a senolytic and should in theory be beneficial, but it doesnt seem beneficial to plants except for coloring them. im confused about this. for example fisetin in strawberies doesnt seem to do anything to protect them from disease or mold. and since strawberries are number one fruit with pesticides, shows its extremely vulnerable to tons of diseases and fungi. i havent studied biochemistry to know any better but by basic logic, if it doesnt seem to benefit the plant that makes it and in fact its presence is highest in a plant thats the easiest to be infected, why in the world would it benefit humans??

[Harkijn]

what i would like to know is, in case of fisetin, it works as coloring agent in fruits like strawberries. how does fisetin benefit those plants as coloring agent and why do you people think that some coloring agent can actually have a positive impact on humans? that is, there is not a single study done on humans to show benefit.

You are quite right and perhaps we in Longecity are too eager to serve as human guinea pigs. However there is some promising research on mice, as for instance described here:

https://www.leafscie...ing-properties/

[Ducky-001]

what i would like to know is, in case of fisetin, it works as coloring agent in fruits like strawberries. how does fisetin benefit those plants as coloring agent and why do you people think that some coloring agent can actually have a positive impact on humans? 

 

Fisetin and other coloring agents main purpose is probably to attract fruit eating animals so the seeds can be spread around. Why would we and other animals eat the brightly colored fruits? Because we have evolved to recognise the benefits of the substances contained in these fruits, and the fruit's have co evolved to contain enough of these substances to attract seed spreaders.

 

Simple logic?

[GABAergic]

i dunno man a lot of poisonous plants are red too. in fact, if i was born in the wild and saw strawberries red color, i would think of it as a warning sign. you know, red is not usually welcoming color like take for example traffic lights. i remember poisonous snakes being reddish in some of the Caribbean.

anyway, anytime i ask about things like fisetin, NR or resveratrol people's reaction at best is, WELL TAKE A LOOK AT THOSE MICE! you know, dont bother me with mice studies anymore. im not 12 and i moved on past them

[Vastmandana]

i dunno man a lot of poisonous plants are red too. in fact, if i was born in the wild and saw strawberries red color, i would think of it as a warning sign. you know, red is not usually welcoming color like take for example traffic lights. i remember poisonous snakes being reddish in some of the Caribbean.
anyway, anytime i ask about things like fisetin, NR or resveratrol people's reaction at best is, WELL TAKE A LOOK AT THOSE MICE! you know, dont bother me with mice studies anymore. im not 12 and i moved on past them

So, I ASSUME you are practicing intermittent fasting and limiting your eating windows to promote atophogy? And you're limiting carbs, of course? If not, you just seem to be bloviating...

No one is suggesting you go out on a scary limb and chug fisetin...Indeed, befor experimenting,I would encourage anyone to get full lab workups and periodically update them as the liver, kidney and other metabolic indicators are kinda important to keep a handle on.

We live in exciting and precarious times... the explosion of information is quite mind blowing. Personally I hope to stick around to see how things work out! At 68 I entered a phase well over a decade ago where longevity and quality of life became a priority and as an infomaniac and science based human, I find the exploding field of metabolic sciences to be VERY timely... I have incorporated MANY new insights into my lifestyle... doing as deep a dive as is possible in all the areas I find are under study...I do my homework and asses risks, given my state of life... and cautiously share my experiences as well as disclose my age... I don't preach about things I don't fully understand like how to ensure a higher rate of uptake...and while I may raise my eyebrows at some of the experimentation of folks on this particular thread...I have been doing fisetin for YEARS and I'm now periodically mega dosing for atophogy...based on current protocols, sometimes during a fast and sometimes between them. I eagerly await REAL insights into improved absorption as is now available for curcumin...


If you're a relatively young person, I can understand your caution...and regardless, some folks are just more cautious than others...Most folks are still shoving garbage in their faces despite the latest science refuting current dogma still being promulgated by idiots everywhere! I'm constantly amazed at the sometimes infantile postings of people who REFUSE to post their age while commenting...I mean, we're dealing with LONGEVITY here! I consider most of these posts irrelevant and/or just trolling as they often seem to come from young folks...dont really know but I come here for science and it seems to me, given the scientific focus of this entire forum, DISCLOSING YOUR AGE is a pretty relevant factor.

I dunno, man... just my reaction...kind cathartic and just needed to vent...apologize if I offended anyone.

Post your friggin ages in your bios, people!

Edited by Vastmandana, 12 April 2019 - 12:15 AM.

[GABAergic]

im actually interested in fisetin because people give it a lot of hype and i dont want to sound rude when i say i dont believe it has any value for humans. and i think the people who keep hyping it, please stop because its immoral to encourage others to waste money on this. so, i read the reviews on amazon too about it and most people say it doesnt do anything for them. the positive reviews might be fake because it has things like "it works" and/or "i think its working". anyone who used this product doesnt even know if it works or not. how can you fall for reviews like "it works" or "i think its working"?  i dont really expect amazing results and everyone to experience dramatic changes but if this thing is able to promote life in some way, it will be very expensive and everyone will go after it. here is what i think, we wait for actual human studies until any of you guys waste your money. so far from clinicaltrials.org there is only one study on old people https://clinicaltria...how/NCT03430037 and it doesnt seem to be going anywhere so far.

no offense, for the people who support this chemical, but please tell me what are your good logical reasons for this? i honestly want to know and dont be upset i ask this and start downvoting me for it. its childish

Edited by GABAergic, 12 April 2019 - 03:23 AM.

[aribadabar]

im actually interested in fisetin because people give it a lot of hype and i dont want to sound rude when i say i dont believe it has any value for humans. and i think the people who keep hyping it, please stop because its immoral to encourage others to waste money on this. so, i read the reviews on amazon too about it and most people say it doesnt do anything for them. the positive reviews might be fake because it has things like "it works" and/or "i think its working". anyone who used this product doesnt even know if it works or not. how can you fall for reviews like "it works" or "i think its working"?  i dont really expect amazing results and everyone to experience dramatic changes but if this thing is able to promote life in some way, it will be very expensive and everyone will go after it. here is what i think, we wait for actual human studies until any of you guys waste your money. so far from clinicaltrials.org there is only one study on old people https://clinicaltria...how/NCT03430037 and it doesnt seem to be going anywhere so far.

no offense, for the people who support this chemical, but please tell me what are your good logical reasons for this? i honestly want to know and dont be upset i ask this and start downvoting me for it. its childish

 

While most people on this forum base their supplementation on science, there are a few who are pioneers and extrapolate the murine studies and start supplementation on that alone ( i.e. without waiting for human studies confirming the findings as they may never happen). Sometimes it pays off other times it is a bust in humans and it does not pan out as anticipated.

That's the situation with fisetin so there are people in both camps.

 

With respect to the reviews - you don't honestly expect those people to run regular detailed bloodwork, take trial notes and functional testing, do you? So virtually all you will have are these anecdotes, even if they are genuine.

Remember, we are at the bleeding edge of science as it is currently available, so you need to decide for yourself: either to wait for human studies or bite the bullet and find for yourself if it works for you as even some "proven" substances work in some people but not in others.

 

Asking over and over again the same thing won't change any of the above in the near future but will virtually guarantee you the downvoting/ignoring.

[male_1978]

 

With respect to the reviews - you don't honestly expect those people to run regular detailed bloodwork, take trial notes and functional testing, do you? 

 

 

Actually, my mother does that. She had cancer (with metastases) and underwent chemotherapy. She gets a detailed analysis of her blood every few weeks, induding markers of inflammation and a lot of other stuff i dont know much about. 

 

 

Its hard to say whether improvements are because of normal recovery or because of a supplement. Of course, as a cancer patient she gets other medicine as well and she takes care of what she eats.

 

But there were two pro-arguments here for using senolytics: First, she does this bloodwork anyway. Second, after chemotherapy she should have more senescent cells than the average person.

 

 

She took a few grams of fisetin within a few days and there were indeed improvements in renal and cardiac function (but not necessarily because of that) and a marker which indicated cell descruction (dont ask me about the name) was higher than normal. Nothing extraordinary however. 

[scooterboy]

I need some help guys ! I just ordered 16 oz of  phosphatidylcholine liposomal from ebay . I am going to mix it with 3000g of fisetin  per day for five days. Being that it is liposomal should I still add Propylene and alcohol to it and you think 16oz would be enough ?

 

Edited by scooterboy, 12 April 2019 - 03:12 PM.

[Vastmandana]

im actually interested in fisetin because people give it a lot of hype and i dont want to sound rude when i say i dont believe it has any value for humans. and i think the people who keep hyping it, please stop because its immoral to encourage others to waste money on this. so, i read the reviews on amazon too about it and most people say it doesnt do anything for them. the positive reviews might be fake because it has things like "it works" and/or "i think its working". anyone who used this product doesnt even know if it works or not. how can you fall for reviews like "it works" or "i think its working"? i dont really expect amazing results and everyone to experience dramatic changes but if this thing is able to promote life in some way, it will be very expensive and everyone will go after it. here is what i think, we wait for actual human studies until any of you guys waste your money. so far from clinicaltrials.org there is only one study on old people https://clinicaltria...how/NCT03430037 and it doesnt seem to be going anywhere so far.
no offense, for the people who support this chemical, but please tell me what are your good logical reasons for this? i honestly want to know and dont be upset i ask this and start downvoting me for it. its childish

First, from this post you don't seem to have a clue what Senolytics are all about...

Second, if you did the slightest bit of homework, you'd FULLY understand the logic of folks here that are incorporating them into their lives... just reading this thread and digesting some of the thoughts of smart folks in the field would make you laugh at some of your own comments...The field of Senolytics is HUGE, NOT pop science...and one of the most exciting focuses of longevity & rejuvination science... Do what you want but blathering nonsense, well, I challenge that... it's not "hype"...

Third...while custom designed big pharma Senolytic concoctions will likely be marketed and naturally expensive, the most powerful natural compound analyzed so far is Fisitin...it is NOT "very expensive"... IT'S FRACKIN CHEAP!

The only relevant point you've made is to discount the few testimonials of folks commenting on how much better they feel... and on commercial site's like Amazon (oy!). Such comments, especially for senoltics, are mostly blather or even if well intended, are potentially placebo as that's not what senolytics do... it's not cocaine or coffee. Additionally, getting funding for widespread, comprehensive and deep studies of such unpatentable substances, especially clinical trials, is challenging, given reduced budgets of agencies and multinational/profit driven corporate influences...I, for one, am not waiting for this to magically occur...

Ok...spent enough time on this...hope you get my points.

Edited by Vastmandana, 14 April 2019 - 02:24 AM.

[Dstein]

Interesting read: Carnosic acid and fisetin combination therapy enhances inhibition of lung cancer through apoptosis induction.

[LarryG]

This study was done in vitro and in vivo in mice.  Carnosic acid is found in Rosemary and Sage.  Carnosic acid can be found by Googling Rosemary Extract.  It's inexpensive.  In mice, 30mg/kg was used, so a conversion rate is needed.  There is no price bar to adding Carnosic acid to the Fisetin dose.  Carnosic acid has high bioavailablility orally in rats (40% in one study) and estimated to be 65% in another.  Non toxic effects seen in humans or rats for Rosemary extract, but in humans, that was for a dose far lower than is contemplated here.  Soluble in ethanol.   http://www.foodstand...s/A1158 SD1.pdf

[maxwatt]

Interesting read: Carnosic acid and fisetin combination therapy enhances inhibition of lung cancer through apoptosis induction.

 

Nice study, thanks.

 

Not just senolytic.  fisetin has multiple effects. 

 

SIRT1 https://www.ncbi.nlm...pubmed/26499075

 

adiponectin https://www.ncbi.nlm...pubmed/25286082

 

https://www.karger.c...FullText/493650

by CJ Liou - ‎2018 - ‎Cited by 2 - ‎Related articles

Sep 20, 2018 - Western blot showed that fisetin reduced SREBP-1c, PPAR-γ, and C/EBPα expression,

 

So any effects individuals note could be due to these other activities, as well as the placebo effect.

[GABAergic]

so amazon doesnt have much choice when it comes to fisetin. doctor's best and two other ones im skeptical of. how do you guys buy your fisetin? alibaba? im not sure ill ever buy it from china though. not only is there a problem of getting reliable studies on it, but finding it in good quality to buy it is difficult.

[GABAergic]

vastmandana, what do you mean fisetin cannot be patented. there are two patents, cognisetin and novusetin. which one are you using?

[LarryG]

As best I can tell, cognisetin and novusetin are sold as memory enhancers.  They are the same thing as the name was changed from cognisetin to novusetin, but according to the ingredients statement, it is only fisetin and fillers.  Their patent is from 2011 but it seems they don't enforce it, perhaps unless it is sold as a cognitive enhancer, but not sure.  Carnosic acid is readily available and cheap, often sold as Rosemary extract with, say, 20% carnosic acid.

 

 

Edited by LarryG, 15 April 2019 - 05:44 PM.

[Vastmandana]

Interesting read: Carnosic acid and fisetin combination therapy enhances inhibition of lung cancer through apoptosis induction.

  

This study was done in vitro and in vivo in mice.  Carnosic acid is found in Rosemary and Sage.  Carnosic acid can be found by Googling Rosemary Extract.  It's inexpensive.  In mice, 30mg/kg was used, so a conversion rate is needed.  There is no price bar to adding Carnosic acid to the Fisetin dose.  Carnosic acid has high bioavailablility orally in rats (40% in one study) and estimated to be 65% in another.  Non toxic effects seen in humans or rats for Rosemary extract, but in humans, that was for a dose far lower than is contemplated here.  Soluble in ethanol.   http://www.foodstand...s/A1158 SD1.pdf

You guys are awesome! Thanks...this is my atophogy week so...ill add a bit once nearing the end of my fast....

[Vastmandana]

Best deal I've found so far...ordered 4... https://www.amazon.c...d/dp/B01K8RV666 (standardized to carnosic acid at 20%)

Ironic, I use to bathe in both Rosemary and Lavender on the farm...we grew loads of it! Nature is sooo amazing! Plan to use a fisetin, bio quercitin, rosemary extract & meta curcumin combo as my fasting atophogy enhancer this month!

Yea, were kinda flying blind... but in the right direction. I'd much prefer THIS than shoving cornflakes, potatoes, pastas and other sugars into my gut, preoccupied with nonsense, which seems to be the preoccupation of most humans...

Ta ta...

Edited by Vastmandana, 15 April 2019 - 08:45 PM.

[GABAergic]

vastmandana, thats cool you posted source for carnosic acid but i asked whats your souce for fisetin.

 

anyway, how much rosemary should one consume to get a good amount of carnosic acid? pills are ok but not when my diet consists of 50% pills and im trying to cut back on them a bit

Edited by GABAergic, 16 April 2019 - 03:18 AM.

[Vastmandana]

If you actually read this thread you'd know... which is something I already suggested

If your diet consists of 50% pills, you've got a real problem and I would suggest not adding to that problem...

Edited by Vastmandana, 17 April 2019 - 02:47 AM.

[GABAergic]

yeah, pills as in supplements. you are probably going to end there too as i see you are quite interested in taking as many as possible for life extension.

anyway, i assume because of your fasting or calorie restriction you are kind of anxious and aggressive in your replies to me. not friendly at all. it makes sense when i read this thread on reddit; https://old.reddit.c...es_anxiety_and/

when you are feeling a bit better, i would appreciate mentioning it one more time for me since im a very busy guy and i only come to this forum once every few days and stay for only 10 mins and i dont have the patience or time to go through 19 pages of posts and use magnifying glass just to seek out where you mention your fisetin source. anyway, try to relax a bit and have a nice day buddy

[Daniel Cooper]

vastmandana, what do you mean fisetin cannot be patented. there are two patents, cognisetin and novusetin. which one are you using?

 

 

Those are "use patents".  They patent the use of a compound (which is unpatentable because it is found in nature or is itself off patent) for a specific purpose.  The person that gets such a patent has the right to market that specific compound for that specific use without competition.  However, other people can make and market the compound for other uses and nothing prevents a purchaser from buying from those sellers and using it for the patented use.  As such, use patents are practically worthless except to put on your product label that your product contains "special patented compounds".

Edited by Daniel Cooper, 19 April 2019 - 01:42 PM.

[GABAergic]

If you are unwilling to spend the time to do the research, I'd suggest to save yourself those 10 mins spent here and use them elsewhere.

Nobody should be expected to spoonfeed you, ok?

 

you might be right. i shouldnt expect answers when i ask people to give me some. hey, better use google and not socialize, discuss, or ask any questions. as you say, its called "spoonfeeding" and its bad

Those are "use patents".  They patent the use of a compound (which is unpatentable because it is found in nature or is itself off patent) for a specific purpose.  The person that gets such a patent has the right to market that specific compound for that specific use without competition.  However, other people can make and market the compound for other uses and nothing prevents a purchaser from buying from those sellers and using it for the patented use.  As such, use patents are practically worthless except to put on your product label that your product contains "special patented compounds".

 

i see. because i do see a lot of so called "patents" on natural ingredients and it always baffled me. in fact, some natural ingredients do not even come in their full natural form anymore but are brand name "patents". its interesting

Edited by GABAergic, 19 April 2019 - 07:09 PM.