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Fisetin: Senolytic!

fisetin senolytic

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#751 lost69

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Posted 21 October 2019 - 09:39 AM

seems like a pain in the ass. what good is this to prolong one's life (supposedly) if you have to hide yourself in your bedroom and avoid exposure to many of life's challenges? when you put it this way, you can easily do that without ever using any senolytic wasting your money on them since just hiding in your bedroom, you automatically have a chance of living longer than those who go out in the world and risk their lives daily by being exposed to challenges. that is, you can just stay home and FAST which is free and proven to extend lifespan. so if we put it in such way, whats the point of bothering with senolytics??

 

senolytics are something you do once a month, not everyday

 

tests to see if fast or senolytics work: high senibility C reactive protein, il6, tnf alpha and these are tests available in every good lab by these you know if inflammation is going down



#752 osris

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Posted 21 October 2019 - 12:40 PM

In Ambivilant's case the anti-clotting mechanism of fisetin was still active 5 days after he took his isolated dosage. In other words, even if you only take it a few days once a month, its anti-clotting activity persists beyond that period -- and for who knows how long after -- maybe until the next dosage is taken a month later. Until this can be confirmed as being not the case, I remain cautious as to fisetin's safety regarding wounds and blood loss. 

 

I'd love to be proven wrong... really I would, as I think the theory behind senolytics is a step forward in life extension.

 

So please, someone, tell me I am wrong.


Edited by osris, 21 October 2019 - 12:41 PM.


#753 Mind

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Posted 21 October 2019 - 06:16 PM

In Ambivilant's case the anti-clotting mechanism of fisetin was still active 5 days after he took his isolated dosage. In other words, even if you only take it a few days once a month, its anti-clotting activity persists beyond that period -- and for who knows how long after -- maybe until the next dosage is taken a month later. Until this can be confirmed as being not the case, I remain cautious as to fisetin's safety regarding wounds and blood loss. 

 

I'd love to be proven wrong... really I would, as I think the theory behind senolytics is a step forward in life extension.

 

So please, someone, tell me I am wrong.

 

Any truly effective senolytic substance should only need to be taken once every few years. There is little data on how effective fisetin is in humans. If it is very effective, then it should NOT need to be taken once a month, maybe once every other year. Taking it more often at this point is an experiment. Your body NEEDS to produce senescent cells in some instances, so constantly taking senolytics is likely to produce unwanted side effects.

 

Our brains are wired to think "more is better". This forum is littered with failed attempts of "more more more....". There is a dose-response curve to almost every therapeutic. Don't be surprised if you have negative side effects when going outside the "curve".

 

I took a course LEFs senolytic activator twice this year. Even for me, it was hard to beat back the natural inclination toward "more is better". I intend to try fisetin or the D+Q product next year, because these are currently theorized to be more effective senolytics.


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#754 sedentary

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Posted 21 October 2019 - 06:49 PM

senolytics are something you do once a month, not everyday

 

tests to see if fast or senolytics work: high senibility C reactive protein, il6, tnf alpha and these are tests available in every good lab by these you know if inflammation is going down

 

so i can go to my regular doctor and ask him to do a test for inflammation concerning c reactive protein, il6, tnf alpha?

something tells me he will look at me funny. not even sure if my doctor knows what those mean. all my primary care physicians knew less than i do. funny how they are doctors with less medical knowledge than me. but then again, they didnt have google in their time so...

SO, perhaps i should go to a private lab and do it myself? any ideas as to where to find one? i cant even use google on this, because im not sure what to look for really...


Edited by sedentary, 21 October 2019 - 06:52 PM.


#755 Mind

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Posted 21 October 2019 - 10:47 PM

so i can go to my regular doctor and ask him to do a test for inflammation concerning c reactive protein, il6, tnf alpha?

something tells me he will look at me funny. not even sure if my doctor knows what those mean. all my primary care physicians knew less than i do. funny how they are doctors with less medical knowledge than me. but then again, they didnt have google in their time so...

SO, perhaps i should go to a private lab and do it myself? any ideas as to where to find one? i cant even use google on this, because im not sure what to look for really...

 

I think you can get those parameters tested for less than $50 through LEF. You just need to have a phlebotomist draw a tube of blood.



#756 lost69

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Posted 21 October 2019 - 10:54 PM

so i can go to my regular doctor and ask him to do a test for inflammation concerning c reactive protein, il6, tnf alpha?

something tells me he will look at me funny. not even sure if my doctor knows what those mean. all my primary care physicians knew less than i do. funny how they are doctors with less medical knowledge than me. but then again, they didnt have google in their time so...

SO, perhaps i should go to a private lab and do it myself? any ideas as to where to find one? i cant even use google on this, because im not sure what to look for really...

 

i m sorry i didn t know there s no freedom where you live.where i live you can have anything tested if you pay

you need a doctor only to get free testing by public healthcare



#757 lost69

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Posted 21 October 2019 - 10:59 PM

Any truly effective senolytic substance should only need to be taken once every few years. There is little data on how effective fisetin is in humans. If it is very effective, then it should NOT need to be taken once a month, maybe once every other year. Taking it more often at this point is an experiment. Your body NEEDS to produce senescent cells in some instances, so constantly taking senolytics is likely to produce unwanted side effects.

 

Our brains are wired to think "more is better". This forum is littered with failed attempts of "more more more....". There is a dose-response curve to almost every therapeutic. Don't be surprised if you have negative side effects when going outside the "curve".

 

I took a course LEFs senolytic activator twice this year. Even for me, it was hard to beat back the natural inclination toward "more is better". I intend to try fisetin or the D+Q product next year, because these are currently theorized to be more effective senolytics.

 

yes this is definitely a problem to keep in mind and this is definitely an experiment

 

although fisetin shouldn t be very potent combinations are potent for sure

 

last month i got an infected wound in the swimming pool, it started as a scratch with no blood and got infected by swimming day after day then took 15days plus oral antibiotic to clear
 



#758 sedentary

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Posted 22 October 2019 - 03:36 AM

i m sorry i didn t know there s no freedom where you live.where i live you can have anything tested if you pay

you need a doctor only to get free testing by public healthcare

 

yeah i live in usa and not Europe. but oh well, whatever! i shouldnt get too aggravated about this now as i have to be concentrated on things at value here which cost much more money than those tests.

anyway, i wish i can return back to Europe and have that good diet naturally, which always makes me feel a bit younger each time. with no confinement and need of requiring lots of advertised pills  *sigh*


Edited by sedentary, 22 October 2019 - 03:41 AM.


#759 osris

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Posted 22 October 2019 - 10:41 AM

Any truly effective senolytic substance should only need to be taken once every few years. There is little data on how effective fisetin is in humans. If it is very effective, then it should NOT need to be taken once a month, maybe once every other year. Taking it more often at this point is an experiment. Your body NEEDS to produce senescent cells in some instances, so constantly taking senolytics is likely to produce unwanted side effects.

 

Our brains are wired to think "more is better". This forum is littered with failed attempts of "more more more....". There is a dose-response curve to almost every therapeutic. Don't be surprised if you have negative side effects when going outside the "curve".

 

I took a course LEFs senolytic activator twice this year. Even for me, it was hard to beat back the natural inclination toward "more is better". I intend to try fisetin or the D+Q product next year, because these are currently theorized to be more effective senolytics.

 

I agree entirely. I am just worried that Ambivilant had blood clotting failure after he took one dose. 

 

I can't recall if he took other supplements at the same time to boost its bio-availability, if he did, then it could be that one of these other supplements in a negative reaction to fisetin caused the clotting failure. I hope so. I have put much hope on fisetin being safe at the dosage frequency you suggest.

 

Maybe Ambivalent was just very unlucky, or his individual body biology is to blame and not fisetin.

 

Ambivalent, if you are out there, please respond.


Edited by osris, 22 October 2019 - 10:48 AM.

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#760 ambivalent

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Posted 22 October 2019 - 10:54 AM

Regarding blood clotting. Unfortunately I am unable to link on this device, but in post 272 there was a SENS article on senescent referenced, which seems to have disappeared, citing the withdrawal of the senolytic Navitoclax because the drug targeted cell survival pathways which clotting depended on. My experience was as stated, with 3 grams of Fisetin, however, around a week later I had a significant dental bleed which clotted fine. I've had no problems since then following a few intermittent large doses; however that might be an issue of timing as I;ve not paid attention to any post-dose wounds. So if there was a problem it was a short window and it might possibly have only occurred subsequent to the first dose. Speculating simplistically, perhaps the larger dental bleed was too strong a signal to ignore? Wart nicks can be small and slow to clot ( this was excessive of course). Anyhow, it is pretty clear senolytics do pose a risk to wound healing, but certainly (for me) if there is a window of clotting impairment it was short lived. Lost69, though, has experienced problems too, though he appears a standard deviation or two out from most of us.

 

@Lost69, I wonder have you considered updating your bio or possibly creating your own senolytic log in this forum? I've not been following events closely and would like a more coherent understanding of your protocols, with a view naturally to giving it a (moderated) go too.      

 

@osris I added olive oil and black pepper to improve bioavailability. Since then just recently a couple of drops of DMSO too. Without problems though it is hard to know if without vulnerability, of course.


Edited by ambivalent, 22 October 2019 - 11:03 AM.


#761 ambivalent

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Posted 22 October 2019 - 11:09 AM

Any truly effective senolytic substance should only need to be taken once every few years. There is little data on how effective fisetin is in humans. If it is very effective, then it should NOT need to be taken once a month, maybe once every other year. Taking it more often at this point is an experiment. Your body NEEDS to produce senescent cells in some instances, so constantly taking senolytics is likely to produce unwanted side effects.

 

Our brains are wired to think "more is better". This forum is littered with failed attempts of "more more more....". There is a dose-response curve to almost every therapeutic. Don't be surprised if you have negative side effects when going outside the "curve".

 

I took a course LEFs senolytic activator twice this year. Even for me, it was hard to beat back the natural inclination toward "more is better". I intend to try fisetin or the D+Q product next year, because these are currently theorized to be more effective senolytics.

 

Well, from anecdotal experience, I am not sure there isn't value a strategy of regular intermittent dosing. As mentioned my knee still weakened after a dose of fisetin the other week, which I took to mean a cell clearance. Perhaps it is the case SCs accumulate more rapidly in certain places, such as arthritic knees.

 

Also, there is a D+Q product, (not protocol)?    


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#762 osris

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Posted 22 October 2019 - 12:47 PM

Regarding blood clotting. Unfortunately I am unable to link on this device, but in post 272 there was a SENS article on senescent referenced, which seems to have disappeared, citing the withdrawal of the senolytic Navitoclax because the drug targeted cell survival pathways which clotting depended on. My experience was as stated, with 3 grams of Fisetin, however, around a week later I had a significant dental bleed which clotted fine. I've had no problems since then following a few intermittent large doses; however that might be an issue of timing as I;ve not paid attention to any post-dose wounds. So if there was a problem it was a short window and it might possibly have only occurred subsequent to the first dose. Speculating simplistically, perhaps the larger dental bleed was too strong a signal to ignore? Wart nicks can be small and slow to clot ( this was excessive of course). Anyhow, it is pretty clear senolytics do pose a risk to wound healing, but certainly (for me) if there is a window of clotting impairment it was short lived. Lost69, though, has experienced problems too, though he appears a standard deviation or two out from most of us.

 

@Lost69, I wonder have you considered updating your bio or possibly creating your own senolytic log in this forum? I've not been following events closely and would like a more coherent understanding of your protocols, with a view naturally to giving it a (moderated) go too.      

 

@osris I added olive oil and black pepper to improve bioavailability. Since then just recently a couple of drops of DMSO too. Without problems though it is hard to know if without vulnerability, of course.

 
Yes, I vaguely remember that post about Navitoclax being withdrawn.
 
Did you have your significant dental bleed around the same time as your shaving cut bleed — i.e. 5 days after your first dose of fisetin?
 
Also, how long did it take before clotting kicked in with the dental bleed? With your shaving cut, I recall you said the bleeding lasted over 4 hours or so. Did the dental bleed clot in less time than that?
 
The discrepancy between the longevity of the shaving cut bleed and the shorter dental bleed is puzzling. It could be explained in the way you explained it—your body “seeing” the dental bleed as being more urgent to clot than the shaving bleed. But that is obviously speculation at this point.
 
Perhaps the clotting problem is dosage related? Maybe a lower dose of fisetin would not disrupt the clotting process?  Or perhaps taking along with the dose of fisetin a supplement that prevents blood thinning (assuming such a supplement is in existence) might reduce any blood loss risk? Though taking such a supplement as the latter, could pose risks of its own.

Edited by osris, 22 October 2019 - 12:57 PM.


#763 osris

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Posted 22 October 2019 - 02:44 PM

Just came across this by a guy called Oleksandr Savsunenko:

 

https://medium.com/@...ce-8dcc171d914a

 

Not sure if it’s particularly relevant to blood clotting but it deals with blood markers in general after taking 3 gram of fisetin for 6 days, so any scientists here might be able to make sense if it all.

 

I’ve quoted it in full below:

 

“I am sharing a story of self-experiment with fisetin — a potential health and longevity-boosting drug, belonging to a novel class of senolytic compounds.

 

Background

 

I am an enthusiast “biohacker” (whatever this means). I am doing regular health check-ups and bloodwork at least two times a year, monitoring critical health and ageing biomarkers, as well as trying various medical interventions to boost my mental and physical state. Also, I can “almost” be considered a professional, as I am M.Sc. biochemist and a PhD in macromolecular chemistry (this means I try not to do stupid things).

 

Senotylics have been taking anti-ageing community by storm. Senescence-based theory of ageing is currently considered as one of the most promising approaches to fight some critical manifestations of ageing.

 

Long story short. There’s a normal ageing process that every cell goes thought. They divide, they live, they die. But, not all of them — sometimes natural mechanism of removing old cells (apoptosis) gets broken and some cells get into the senescence phase. That’s a state of “limbo” — cell continues to live, consume resources, but produces no useful functions and pollutes surrounding space with chemical markers of age. Time goes by, body continues to accumulate those cells and impact becomes more and more visible — ageing.

 

The idea of senolytic therapy is pretty simple — let’s force those cells to die and remove them out of the body. This should really improve our health.

 

As I am writing this article Phase I of trials testing a most well-known combination of senolytics is in progress and even some very preliminary results made available.

 

Recent publication showed that a compound called “fisetin” has very pronounced senolytic properties. A high-dose acute intervention was shown to promote cleansing of senescent cells in mouses and human tissues.

 

And, by a great coincidence, fisetin is not an extremely expensive research chemical but rather a well-known flavonoid. And you can buy it online as a supplement.

 

Whaaaat? If this is such a great compound and it’s sold online, why nobody noticed any great health-promoting effects? One of the explanations is simple — the dosage. Researched used much higher doses of fisetin.

 

Anyway, I decided to give it a try.

 

The Experiment

 

I did a traditional bloodwork check-up based on Longevity Panel 1.4, containing major biomarkers a few weeks before I started the experiment.

 

This is a diagnostic panel developed by Russian longevity community, and I wasn’t able to find an English website to link you, guys. So, here’s my adjusted version of human blood biomarkers for longevity prediction and general health assessment.

 

Alanine transaminase

Vitamin B12

Albumine

Vitamin D (calciferol)

Folic acid

Ca 2+/Na 2+/K+/Cl-

Insulin

Creatinine

Uric acid

C-reactive proteins

T3 free / T4 free/ TSH

Ferritin

Lipid profile + cholesterol

HOMA-IR

HbA1

 

What did I expect from successful treatment? I had no idea, to be honest. Based on preliminary results from a similar experiment going on in Russian biohackers community I was looking for the dramatic change in cystatin C.

 

During my 6 day treatment, especially on the first and second day, I felt really strange — kind of light-headed and dizzy, also extremely thirsty and dehydrated (signs of dehydration are clearly seen even after two weeks when I did post-intervention checkup).

 

During the treatment, the most pronounced subjective effect was a change in skin condition. My wife noticed a fast and rapid change in my skin quality just in a few days. It became much firmer, hydrated (despite general dehydration) and smooth. I was very disappointed that I haven’t found a way to quantify this change. My next experiment will definitely include in-depth skin analysis using professional dermatologist equipment.

After two weeks from the last dose, I repeated my bloodwork, just to find that none of the biomarkers changed in a better direction and some just got slightly worse.

 

Conclusions

 

Other people experimenting with fisetin also didn't noticed any change in blood markers, as well as preliminary results from stage 1 clinical trial of another senolytics regiment (D+Q).

 

Potential explanations:

 

  • it takes more time to develop changes in blood
  • compound is ineffective in humans
  • we should focus more on monitoring functional characteristics, like VO2 max, heart rate variability, pulse wave speed, etc.
  • we need more people and more data”

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#764 aribadabar

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Posted 22 October 2019 - 04:46 PM

For a PhD he should have known that HED calc requires DIVISION, not multiplication, by 12.3 the error resulting in order of magnitude difference...

 

 


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#765 OP2040

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Posted 22 October 2019 - 05:02 PM

uhm how is this a bad habit if you have wine in moderation? if anything, it probably helped boost your life longer than all the curcumin you have been consuming. https://en.wikipedia...content_in_wine check out the list of polyphenols in wine. so many of them are scarce or modestly distributed in fruits and vegetables but are all present in good quality, oak aged red wines. whats the list of polyphenols on turmeric? it seems besides curcuminoids it doesnt have a huge list of contents.

 

 

I agree with the spiirit of this as my entire point is that "giving up everything" is a really morbid way to extend life or healthspan.  However, I'm not sure if you've been reading the news this year on alcohol, but there are a couple studies claiming that there are not only no benefits but at least some harm at any level of alcohol consumption.

 

Here's an example of the new media being pumped out about alcohol in the last couple years:

https://www.bbc.com/...ne-good-for-you

 

 

My point is in agreement with you in spirit.  We shouldn't bother giving up modestly damaging pleasures for the barely relevant health or lifespan effects that many of these studies demonstrate.  Furthermore, there has been so much research on diet, exercise and metabolism and the surprisingly small benefits they provide to lifespan and healthspan.  At this point, more of these studies is a complete waste of time and money.  Literally everyone knows what a basic healthy lifestyle consists of, but there is much ignorance about the actual strength of lifestyle interventions, which are actually quite weak.

 

We need to constantly be pivoting away from these mundane and largely negative (in the sense of preventing damage) lifestyle interventions, and toward regeneration, rejuvenation and total control of the body.  We now know it is likely possible to have this much control, but we still have large parts of academia wasting our time with worthless studies on polyphenols or some such.  

 

As for senescent cells, it's a great intervention even though it is still only clearing out damage and not necessarily rejuvenating.  This is because it will come in pill and not lecture form. But for what we truly want we will need to do something more like what AGEx is attempting, true regeneration based on the examples we already have, embryogenesis or regenerating animals.  These examples show that the answers are in epigenetics and dna repair mainly.  After more than a decade the "Hallmarks of Aging" paper still holds up as the way forward, as opposed to SENS. And it points toward the idea that senescent cell removal, while extremely exciting, is still a secondary cause of aging.  Lets get back to the primaries please.


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#766 OP2040

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Posted 22 October 2019 - 05:16 PM

As if to underline and emphasize my point, hot off the presses:

 

https://www.mpg.de/1...lifelong-affair

 

The gold standard of fad metabolic nonsense, calorie restriction, doesn't even work in old age when it is needed most.  And I'm pretty sure no one places humans from age 0-18 on calorie restricted diets, when it is most effective.  

 

It makes sense because calorie restriction itself feeds off of evolutionary pressure, so it would not do anything in the selection shadow or old age. BTW, old age for humans in evolutionary terms  probably starts as early as the 40's. I apologize as this is not the right thread for these rants, but it is tangentially relevant.


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#767 osris

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Posted 22 October 2019 - 05:44 PM

OP2040, just out of interest, when you took fisetin, did you experience any lack of blood clotting problems like Ambivalent did?

 

 


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#768 ambivalent

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Posted 22 October 2019 - 05:46 PM

To clarify, the dental bleed was a week after the shaving cut.


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#769 osris

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Posted 22 October 2019 - 05:49 PM

PS to my last post:

 

Sorry for my harping on about the lack of blood clotting issue, but I think it is a really important issue, and is likely to put people off from taking fisetin.


To clarify, the dental bleed was a week after the shaving cut.

 

How long did the bleed last?


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#770 OP2040

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Posted 22 October 2019 - 05:56 PM

OP2040, just out of interest, when you took fisetin, did you experience any lack of blood clotting problems like Ambivalent did?

 

 

Not at all. I take Vitamin K2 so maybe that's a factor.  But I can't say for sure that Fisetin did anything at all in my case.  I'm in agreement with most everyone else that true senescent cell removal should have fairly obvious health effects.  So it makes me question Fisetin's bioavailability.  We'll see how the D+Q works when I get it.


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#771 sedentary

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Posted 22 October 2019 - 06:34 PM

As if to underline and emphasize my point, hot off the presses:

 

https://www.mpg.de/1...lifelong-affair

 

The gold standard of fad metabolic nonsense, calorie restriction, doesn't even work in old age when it is needed most.  And I'm pretty sure no one places humans from age 0-18 on calorie restricted diets, when it is most effective.  

 

It makes sense because calorie restriction itself feeds off of evolutionary pressure, so it would not do anything in the selection shadow or old age. BTW, old age for humans in evolutionary terms  probably starts as early as the 40's. I apologize as this is not the right thread for these rants, but it is tangentially relevant.

 

thats a bummer but it has been making sense to me before such article. of course old people cannot just rely on calorie restriction as they are frail and need all the vitamins, protein, fat they can get as they become older and sicker.

but how do you know 40 is the last invitation for CR ? ill think maybe at least 50



#772 sedentary

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Posted 22 October 2019 - 06:37 PM

Not at all. I take Vitamin K2 so maybe that's a factor.  But I can't say for sure that Fisetin did anything at all in my case.  I'm in agreement with most everyone else that true senescent cell removal should have fairly obvious health effects.  So it makes me question Fisetin's bioavailability.  We'll see how the D+Q works when I get it.

 

quercetin is everywhere but how are you planning on acquiring dasatinib ? hard to find cancer medication thats expensive. and even if prescribed, not sure insurances can cover it either. but good luck getting prescribed in the first place!

 

"Severe side effects may include bleeding, pulmonary edema, heart failure, and prolonged QT syndrome"

so it has the same side effect as fisetin hmm... must be the senescent thing going

anyway i got too fed up with all the negative reports on fisetin so far in this thread so i decided to dump it.


Edited by sedentary, 22 October 2019 - 06:39 PM.


#773 OP2040

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Posted 22 October 2019 - 07:23 PM

sedentary,

love the handle btw.   

 

40 is pretty old in evolutionary terms.  Even if it is later, why should we go for solutions that only work for a small minority of the population.  We need interventions that robustly reverse aging.  There are a bunch of words and phrases like "could cure" which make me stop reading a news article immediately.  Another prominent one is when something is said to "slow down the rate of decline" of some horrific disease.  That's a shamefully low bar and one that we should no longer need to accept.

 

Dasatinib can be acquired.  The side effects have been discussed on the forum, and the consensus seems to be that they are an artifact of it's typical use in cancer patients.  For the short term administration needed for senolytic effect it should not be a problem.  Aside from that there seems to be a bunch of people here that have tried it with none of those issues.



#774 Kentavr

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Posted 22 October 2019 - 07:26 PM

I agree with the spiirit of this as my entire point is that "giving up everything" is a really morbid way to extend life or healthspan. However, I'm not sure if you've been reading the news this year on alcohol, but there are a couple studies claiming that there are not only no benefits but at least some harm at any level of alcohol consumption.

Here's an example of the new media being pumped out about alcohol in the last couple years:
https://www.bbc.com/...ne-good-for-you

As for senescent cells, it's a great intervention even though it is still only clearing out damage and not necessarily rejuvenating. This is because it will come in pill and not lecture form. But for what we truly want we will need to do something more like what AGEx is attempting, true regeneration based on the examples we already have, embryogenesis or regenerating animals. These examples show that the answers are in epigenetics and dna repair mainly. After more than a decade the "Hallmarks of Aging" paper still holds up as the way forward, as opposed to SENS. And it points toward the idea that senescent cell removal, while extremely exciting, is still a secondary cause of aging. Lets get back to the primaries please.


I completely agree with you. Senolitics are the wrong way.

This is more like treating an existing disease than preventing aging.

We need:

1. Strengthen mitophagy, as well as cleaning cells from debris - autophagy (Rapamycin, Spermidine)

2. Increase the number of stem cells (metformin, protocol "Turnbuckle C60evoo", etc.)

3. Reduce inflammation (telmisartan)

4. Support the catecholamine system to reduce the degradation of neurons (deprenyl)

5. Support the expression of microRNAs responsible for youth (I don't know how yet).

6. Carry out an epigenetic rollback and strengthen the immune system (TRIIM study protocol)

7. Improve DNA repair and activate sirtuins (sublingual use of the drugs NMN and NAD +)

Senolitics are a weapon of the 4th-5th stage of application, when some of the processes went very far and other methods could not solve them.

Edited by Kentavr, 22 October 2019 - 07:43 PM.

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#775 Rays

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Posted 22 October 2019 - 08:25 PM

Does anybody know the chemical formula of the Novusetin fisetin that is used in Swanson Ultra Fisetin?
I'm wondering whether it's the four hydroxy version used in the mice studies (3,7,3',4'-Tetrahydroxyflavone) or the three hydroxy version as sold by Purebulk.
The trademark holder's website does not tell this:
 
 

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#776 OP2040

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Posted 22 October 2019 - 08:33 PM

I don't think it will be that complicated once we have it all figured out.  Epigenetic reprogramming will cover 90% of it.  Reprogramming is already known to rejuvenate the entire cell, including but not limited to:

1. restoring telomere length

2. restoring proteostasis (through lysosomes)

3. restoring mitochondrial function

4. reverting senescent cells (rather than eliminating)

5. restoring stem cells

 

That leaves only questions about the ECM and genomic stability, both of which should at least be partially restored.


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#777 lost69

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Posted 23 October 2019 - 09:26 AM

Regarding blood clotting. Unfortunately I am unable to link on this device, but in post 272 there was a SENS article on senescent referenced, which seems to have disappeared, citing the withdrawal of the senolytic Navitoclax because the drug targeted cell survival pathways which clotting depended on. My experience was as stated, with 3 grams of Fisetin, however, around a week later I had a significant dental bleed which clotted fine. I've had no problems since then following a few intermittent large doses; however that might be an issue of timing as I;ve not paid attention to any post-dose wounds. So if there was a problem it was a short window and it might possibly have only occurred subsequent to the first dose. Speculating simplistically, perhaps the larger dental bleed was too strong a signal to ignore? Wart nicks can be small and slow to clot ( this was excessive of course). Anyhow, it is pretty clear senolytics do pose a risk to wound healing, but certainly (for me) if there is a window of clotting impairment it was short lived. Lost69, though, has experienced problems too, though he appears a standard deviation or two out from most of us.

 

@Lost69, I wonder have you considered updating your bio or possibly creating your own senolytic log in this forum? I've not been following events closely and would like a more coherent understanding of your protocols, with a view naturally to giving it a (moderated) go too.      

 

@osris I added olive oil and black pepper to improve bioavailability. Since then just recently a couple of drops of DMSO too. Without problems though it is hard to know if without vulnerability, of course.

 

my usual senolytic protocol started about 1 year ago: 1g quercitin, 0.6g fisetin, 100mg apigenin, 100mg delta/gamma tocotrienols (sometimes added 1g IP6) BP got normal and i never had problems but this can be coincidence

 

then i added tunrbuckle apoptosis protocol to that.

time -1 2g NR to induce state of fission

time 0 2g curcumin phytosome, 1g quercetin phytosome,liposomal resveratrol 250mg,sodium butyrate 1g every half an hour for 4 hrs), my protocol (apigenin probably not necessary but i took it to finish the bottle i bought)

 

time 4 leucine and threonine 5g

this senolytic protocol is followed for 2 days after 3days of stemcell renewal protocol.

1g dlimonene after every meal for laryngeal reflux is always taken/never stopped whatever protocols

 

my protocol had gdf11 too but i stopped it long before making this senolytic protocol mid agust of this year because it is like overdosed now even on very low dose 0.05ng per week

 

i also take other vitamins everyday but i dont think this has any extra effect: vit d3 10.000iu, vit A retinoic acid 10.000iu, magnesium, folate, vit b12, vit k2 mk4 and mk7,selenium, zinc,

macuguard fPhospholipids,free lutein, meso-zeaxanthin & trans-zeaxanthin], mixed carotenoids,Saffron extract (stigma),Natural astaxanthin,C3G

 

on periods not on this stemcell/senolytic protocol i add to the usual vitamins: aswaghanda, milk thistle, fish oil, blackseed oil, curcumin, 4mg melatonin at 22-23pm


Edited by lost69, 23 October 2019 - 09:56 AM.

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#778 osris

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Posted 23 October 2019 - 09:48 AM

 

 

"Severe side effects may include bleeding, pulmonary edema, heart failure, and prolonged QT syndrome"

 

Is this referring to dasatinib/and or quercetin?



#779 osris

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Posted 23 October 2019 - 09:56 AM

Not at all. I take Vitamin K2 so maybe that's a factor.  But I can't say for sure that Fisetin did anything at all in my case.  I'm in agreement with most everyone else that true senescent cell removal should have fairly obvious health effects.  So it makes me question Fisetin's bioavailability.  We'll see how the D+Q works when I get it.

 

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?



#780 osris

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Posted 23 October 2019 - 10:22 AM

Ambivalent, I forgot to ask if you had your shaving cut after the very first time you did the fisetin “protocol” or after the second or subsequent ones? 
 
If it didn’t happen after the first one, then the chances are that the lack of blood clotting might not be connected to fisetin at all. For if lack of blood clotting was a potential issue with fisetin (and I can’t find any information or research on fisetin that even mentions potential lack of blood clotting issues), it would have surely manifested itself after the very first time you used it. 
 






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