1079 replies to this topic

[Mind]

Fair enough, I'm certainly hoping that it does exactly that.  But at the least we can all agree that it is still a stopgap, and LEV will not happen with either senolytics or the nutrient sensing pathways.  It will be one of the other hallmarks or some third party intervention organ replacement.  My money is on epigentics and partial reprogramming.   In any case, the argument can be made that we should stop spending so much time on senolytics and sirtuins, and move on a bit to the vanguard. After all, these are becoming mature technologies and I'm convinced they will be mastered in most of our lifetimes.  So all we have to do is cautiously but optimistically follow what the many startup companies and research groups are doing and upgrade year-on-year.  But as vanguards, the bulk of our energy should be on the cutting edge stuff, not endlessly fine-tuning of established technologies.  All that I want left of the senolytics space is a test and that's the only reason I pay attention to this thread.  Outside of that, I'm sure the studies will keep rolling in, and within a few years we will have the senescent cell hallmark checked off.

 

Of course, senescent cells are not the be-all end-all of aging. However, they could be one of the key contributors to aging. At SRF they are currently speculating as to how much senescent cells interact with other types of damage, or how much "cross-talk" there is between different types of aging damage.

 

Do they (types of aging damage) amplify each other, act in isolation, etc...

 

Given that senolytics (like fisetin) are relatively cheap, have known and minimal side effects, and are very effective in animal models, it makes sense to me to give them a try, while other therapies are developed.

Edited by Mind, 15 October 2019 - 05:13 PM.

[Kentavr]

Of course, senescent cells are not the be-all end-all of aging. However, they could be one of the key contributors to aging. At SRF they are currently speculating as to how much senescent cells interact with other types of damage, or how much "cross-talk" there is between different types of aging damage.

Do they (types of aging damage) amplify each other, act in isolation, etc...

Given that senolytics (like fisetin) are relatively cheap, have known and minimal side effects, and are very effective in animal models, it makes sense to me to give them a try, while other therapies are developed.

Mind, senolytics are a good remedy when you are between 45 and 65 years old.

If you are already 65-80 years old, then this is dangerous. Reason: Too many old cells. If they die in one moment, then this can cause permanent damage.

Such damage has already been described on this forum: a person took quercetin and tocotrienols, as a result of which he received permanent damage to his hearing.

For a very elderly person, effective mixtures of senolitics are very dangerous.

Edited by Kentavr, 15 October 2019 - 07:28 PM.

[sedentary]

what are tocotrienols and senolytism to do with each other

[Kentavr]

what are tocotrienols and senolytism to do with each other

Senolytic:
https://en.m.wikiped.../wiki/Senolytic
Tocotrienol:
https://en.m.wikiped...iki/Tocotrienol

[sedentary]

Senolytic:
https://en.m.wikiped.../wiki/Senolytic
Tocotrienol:
https://en.m.wikiped...iki/Tocotrienol

 

yes, very informative. i already knew what senolytic and tocotrienol is. thanks for reminding me though. its always good to be reminded of things as one gets old and forgettable. bless your heart, son.

so anyway, what are tocotrienols and senolytism have to do with each other?

Edited by sedentary, 16 October 2019 - 02:34 AM.

[Kentavr]

yes, very informative. i already knew what senolytic and tocotrienol is. thanks for reminding me though. its always good to be reminded of things as one gets old and forgettable. bless your heart, son.
so anyway, what are tocotrienols and senolytism have to do with each other?

Tocotrienols initiate apoptosis. Especially gamma tocotrienol.

https://www.ncbi.nlm...enol apoptosis

Together with other senolytics, they show very good synergy, which can have bad consequences in a very old body.

Edited by Kentavr, 16 October 2019 - 03:47 AM.

[pamojja]

Tocotrienols initiate apoptosis. Especially gamma tocotrienol.

https://www.ncbi.nlm...enol apoptosis

Together with other senolytics, they show very good synergy, which can have bad consequences in a very old body.

 

From in vitro studies of one compound to conjecture applyed to other compounds at a specific age range? Are you serious?

 

One could just as well say that senescent cells 'can have bad consequencs in a very old body'.
 

[Kentavr]

From in vitro studies of one compound to conjecture applyed to other compounds at a specific age range? Are you serious?

One could just as well say that senescent cells 'can have bad consequencs in a very old body'.

"γ-TT and δ-TT have the highest anti-cancer activities and target common molecular pathways involved in the inhibition of the cell cycle, the induction of apoptosis and autophagy, and the inhibition of invasion, metastasis, and angiogenesis. Future directions should focus on further investigating how γ-TT and δ-TT (solely or in combination) induce anti-cancer molecular pathways when used in the presence of conventional chemotherapeutic drugs."

https://www.ncbi.nlm...ubmed/31016386/

e. t. c., on this subject a lot of research.

[Oakman]

"γ-TT and δ-TT have the highest anti-cancer activities and target common molecular pathways involved in the inhibition of the cell cycle, the induction of apoptosis and autophagy, and the inhibition of invasion, metastasis, and angiogenesis. Future directions should focus on further investigating how γ-TT and δ-TT (solely or in combination) induce anti-cancer molecular pathways when used in the presence of conventional chemotherapeutic drugs."

https://www.ncbi.nlm...ubmed/31016386/

e. t. c., on this subject a lot of research.

 

I want my 'very old body' to not get cancer. So what's wrong with Tocotrienols if they do what is said in the link (actually it says studies needed)? I also want to get rid of 'bad (misbehaving) cells'. I don't care if I'm 40 or 90 yrs old, I want whatever cells are left to be the best they can be, without being dragged down my the used up ones. What am I missing in your argument?

[Kentavr]

I want my 'very old body' to not get cancer. So what's wrong with Tocotrienols if they do what is said in the link (actually it says studies needed)? I also want to get rid of 'bad (misbehaving) cells'. I don't care if I'm 40 or 90 yrs old, I want whatever cells are left to be the best they can be, without being dragged down my the used up ones. What am I missing in your argument?

If your neurons die from the Senolitics, because they are too old and you are 90 years old, perhaps you will remember this post (if at that time you still have memory)

When there are too many old cells in a very old age, senolitics can do worse than they used to.

"No old neurons - no problem."

Edited by Kentavr, 16 October 2019 - 03:54 PM.

[Oakman]

If your neurons die from the Senolitics, because they are too old and you are 90 years old, perhaps you will remember this post (if at that time you still have memory)

When there are too many old cells in a very old age, senolitics can do worse than they used to.

"No old neurons - no problem."

 

Well, if the old neurons aren't working anyway (at any age), what's the problem if you get rid of them?

What they ARE doing is getting in the way, gumming up the works, and producing toxic molecules.

In fact, people can live and function perfectly well with literally, 'half a brain'. That's a lot of cells gone.

I doubt clearing a few bad neurons with synolitics is going to make matters any worse.

 

A garden grows best when the weeds and dead and dying undergrowth is removed. Same for my brain.

[Kentavr]

Well, if the old neurons aren't working anyway (at any age), what's the problem if you get rid of them?
What they ARE doing is getting in the way, gumming up the works, and producing toxic molecules.
In fact, people can live and function perfectly well with literally, 'half a brain'. That's a lot of cells gone.
I doubt clearing a few bad neurons with synolitics is going to make matters any worse.

A garden grows best when the weeds and dead and dying undergrowth is removed. Same for my brain.

A poorly functioning neuron is better than not having it, but there is nothing to replace it with.

In addition, cell death is a very big price for the old organism.

It often happens that a cell has a lot of waste that cannot be disposed of. In this case, it is better to enhance autophagy with rapamycin (6 mg / week, 1 time per week every week for several months).

Or the cell suffers from defective mitochondria. In this case, it is better to conduct a protocol developed by a forum member under the nickname "Turnbuckle" to reduce the number of defective mitochondria.

Cell death from senolytics is an expensive solution for a very old organism.

Check out the relevant threads in this forum.

[Harkijn]

A note of caution here. If people really worry that they are too frail for this rather mild and incidental cellular cleanup they should confer with a trusted medical doctor. Do not put your trust in  regimens asserted here and elsewhere on the internet.

[Kentavr]

A note of caution here. If people really worry that they are too frail for this rather mild and incidental cellular cleanup they should confer with a trusted medical doctor. Do not put your trust in regimens asserted here and elsewhere on the internet.

Everyone decides what information to trust, as well as what to do. Each has its own head.

Some simply will not be able to live up to the time when officially approved drugs for prolonging life appear. They are very many years old.

Edited by Kentavr, 17 October 2019 - 09:04 AM.

[wbtmwbwm]

I did a three day experiment.

Fasting on day one and two.

Day 1:  1g of fisetin + 1g quercetin + 1g resveratrol + 500mg curcumin

Day 2:  2g of fisetin + 2g quercetin + 1g resveratrol + 500mg curcumin

Day 3:  2g of fisetin + 2g quercetin + 1g resveratrol + 500mg curcumin

I dissolved f+q in olive oil and had a scoop of lecithin (~3-4g)

Also I did my own kind of hyperthermia treatment on day 2 using a sauna blanket.

 

Result: pretty much none other than being superdisgusted by my fisetin/quercetin/olive oil mix which was a bit hard to get down.

I have the impression that I could have swallowed 20g or more of the fisetin and it wouldn't have had any effect. Doesn't seem to get absorbed.

Also I'm taking curcumin for about 2 years. Maybe that did something already.

Age: 49

 

I might give it another go with liposomal finesitin.

[OP2040]

 

Result: pretty much none other than being superdisgusted by my fisetin/quercetin/olive oil mix which was a bit hard to get down.

I have the impression that I could have swallowed 20g or more of the fisetin and it wouldn't have had any effect. Doesn't seem to get absorbed.

Also I'm taking curcumin for about 2 years. Maybe that did something already.

Age: 49

 

I might give it another go with liposomal finesitin.

 

 

Are you one of these forum super-athletes with a resting pulse of 40 who is trying to increase your marathon time by a few percentage points.  Or do you actually have real, measurable aging disease states at hand?

 

most likely it's something in the middle like the usual "aches and pains".  But the super-athlete hypochondriac struggle is real.

 

Anyway, I mean to make a serious point but all in lightheartedness and fun, so please don't take it the wrong way.  I have had the exact same experience as you.  I do have a couple measurable disease states to go on and the exact same mix as you are trying didn't move the needle one bit.  I'll continue to take Fisetin very intermittently because it's expensive, and Curcumin regularly. Mainly because innumerable studies have shown their benefit and I'm convinced there will be long-term benefits if not dramatic short-term ones.  

 

Having said all that, I've been won over by the D+Q people who claim that this combo actually has tweaked their physiology to a very noticeable degree.  Almost every good senolytic study in mice is with D+Q and now we have one in humans too.  So I think it's time to make the switch.  There are needles to move.... and life is short.

 

As a side note, and for fun, do any of you guys have any bad habits.  I'll go first.  Arguable not a bad habit in moderation, but I sure love my wine .... in moderation.  Again, life is short and it's foolhardy  to give up all pleasures in pursuit of .5 years life extension.  Might do it for 10-20 years though (in hopes of making it to LEV)

Edited by OP2040, 18 October 2019 - 07:15 PM.

[sedentary]

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 wanted to ask you wbtmwbwm, for those 2 years you have been taking curcumin, whats the main positive thing you have noticed? if you say joint support or immune support, i can name 5 to 10 things which have long history of proof they help with those issues. not sure what else would you expect from turmeric really.

Edited by sedentary, 18 October 2019 - 09:11 PM.

[sedentary]

i got some fisetin. what am i suppose to feel by the end of it to know its authentic ?

 

here are the issues i have;

easy bruising

fatigue general;

mental discomfort relation to anxiety and severe depression

physical fatigue due to exercise

pain in my joints, hands, legs, feet and throughout my whole body

various other issues like likehood for seizures and mental dissociation and discomfort

 

any idea it might benefit me for any of those issues long term? i hope so. i just spent lots of money. i did same with NR few years back because of heavy advertisement on forums like this. i lost about 300 dollars on NR with no benefit. perhaps i brought wrong product and deceived myself only. but im optimist! perhaps this works, hopefully. i mean why would people waste so much of their time lying??

Edited by sedentary, 20 October 2019 - 04:48 AM.

[lost69]

"γ-TT and δ-TT have the highest anti-cancer activities and target common molecular pathways involved in the inhibition of the cell cycle, the induction of apoptosis and autophagy, and the inhibition of invasion, metastasis, and angiogenesis. Future directions should focus on further investigating how γ-TT and δ-TT (solely or in combination) induce anti-cancer molecular pathways when used in the presence of conventional chemotherapeutic drugs."

https://www.ncbi.nlm...ubmed/31016386/

e. t. c., on this subject a lot of research.

 

my senolytic protocol had a clear boost when i added γ-TT and δ-TT, my BP lowered with the other products but there was a tendency to increase again after 7 days of no senolytics, when i added γ-TT and δ-TT my BP became low pressure like when i was a teen (around 90/60-70) and it stays there even if i use no senolytics for more than 7 days

so it definitely worked for me on epithelial cells

[Mind]

i got some fisetin. what am i suppose to feel by the end of it to know its authentic ?

 

here are the issues i have;

easy bruising

fatigue general;

mental discomfort relation to anxiety and severe depression

physical fatigue due to exercise

pain in my joints, hands, legs, feet and throughout my whole body

various other issues like likehood for seizures and mental dissociation and discomfort

 

any idea it might benefit me for any of those issues long term? i hope so. i just spent lots of money. i did same with NR few years back because of heavy advertisement on forums like this. i lost about 300 dollars on NR with no benefit. perhaps i brought wrong product and deceived myself only. but im optimist! perhaps this works, hopefully. i mean why would people waste so much of their time lying??

 

Get an aging biomarker test or another test of biological function (before and after). It is the only way to know for sure and remove subjectivity.

[poonja]

Trying to locate source for the TTs mentioned by lost69.  Could anyone here be of help.  The tocotrienols I found do not reference y-ft and the other YY referred to.

[lost69]

Trying to locate source for the TTs mentioned by lost69.  Could anyone here be of help.  The tocotrienols I found do not reference y-ft and the other YY referred to.

 

you can find using the term tocotrienols, i use delta and gamma tocotrienols from swanson

 

https://www.swansonv...itional-details

 

it is important not to search for vitamin E or tocopherols because there are so many products with mixed delta, gamma tocotrienols and tocopherols while the senolytic benefit is only from tocotreinols.i use 100mg, i never checked studies or tried higher doses since this dose worked already.i also tried 1g fisetin but not feeling well so i kept it to 0.6g

Edited by lost69, 20 October 2019 - 01:50 PM.

[poonja]

Thank you very much for your prompt response.  I was confused bby the TT and T? designation.  I hope I have a similar experience as you.

[Nate-2004]

I did a three day experiment.

Fasting on day one and two.

Day 1:  1g of fisetin + 1g quercetin + 1g resveratrol + 500mg curcumin

Day 2:  2g of fisetin + 2g quercetin + 1g resveratrol + 500mg curcumin

Day 3:  2g of fisetin + 2g quercetin + 1g resveratrol + 500mg curcumin

I dissolved f+q in olive oil and had a scoop of lecithin (~3-4g)

Also I did my own kind of hyperthermia treatment on day 2 using a sauna blanket.

 

Result: pretty much none other than being superdisgusted by my fisetin/quercetin/olive oil mix which was a bit hard to get down.

I have the impression that I could have swallowed 20g or more of the fisetin and it wouldn't have had any effect. Doesn't seem to get absorbed.

Also I'm taking curcumin for about 2 years. Maybe that did something already.

Age: 49

 

I might give it another go with liposomal finesitin.

 

Why no piperine? That would likely help the most. Fats only do so much. 

[osris]

My experience with Fisetin was indicative of one, a known senolytic effect - delayed wound healing: a minor nick on a wart took 5.5hours to clot. 

 

 

This is very bad news. It means that if one where to get a serous injury that bled profusely, one could die quicker than normally.

 

Come to think of it, a usually non-serious injury—such as an upper tooth extraction—could lead to tremendous blood loss and death.

 

I’m surprised no one here has thought of this potential risk.

 

It makes me very reluctant to try fisetin.

 

Can any one reassure me that Ambivilant’s experience is a one off?

Edited by osris, 20 October 2019 - 06:23 PM.

[lost69]

This is very bad news. It means that if one where to get a serous injury that bled profusely, one could die quicker than normally.

 

Come to think of it, a usually non-serious injury—such as an upper tooth extraction—could lead to tremendous blood loss and death.

 

I’m surprised no one here has thought of this potential risk.

 

It makes me very reluctant to try fisetin.

 

Can any one reassure me that Ambivilant’s experience is a one off?

 

senolytic treatment (when high doses and many senolytics are combined) is best on weekends when you can rest

not when there s an illness or a surgery planned
 

[sedentary]

Get an aging biomarker test or another test of biological function (before and after). It is the only way to know for sure and remove subjectivity.

 

interesting. good idea actually. not sure where to find such thing though. google search confuses me even more. how did you come up with this, you must have something on your mind Mind, as to recommend?

Edited by sedentary, 21 October 2019 - 02:04 AM.

[sedentary]

you can find using the term tocotrienols, i use delta and gamma tocotrienols from swanson

 

https://www.swansonv...itional-details

 

it is important not to search for vitamin E or tocopherols because there are so many products with mixed delta, gamma tocotrienols and tocopherols while the senolytic benefit is only from tocotreinols.i use 100mg, i never checked studies or tried higher doses since this dose worked already.i also tried 1g fisetin but not feeling well so i kept it to 0.6g

 

it seems swanson uses DeltaGold. that is popular annato extract brand and its sold everywhere by different companies. i used to get this one https://www.amazon.c...7&s=hpc&sr=1-12 but its more expensive because its 125mg per dose unlike swanson's 50mg. from the studies, you need higher dose so i suppose paying that extra price is no biggie. anyway, i stopped using it because i never experienced anything significantly positive and over time the money amounts. i suppose now with its proposed senolytic effect i might restart but ill definitely need at least minimum 100mg per dose to start. maybe get swanson and use 2 caps a day.

 

btw i also got red palm fruit oil which naturally contains tocotrienols. any idea if naturally sourced tocotrienols from red palm fruit oil are better idea? its much cheaper https://www.amazon.c...71623982&sr=8-4 if you buy two it will last you a long time since its only a tablespoon contains probably 25mg of tocos. so ill assume several tablespoons a day, you are still saving money. most importantly, its naturally source based and i assume it might be better on fact its bound with other vital nutrients. im always skeptical when it comes to processed things because they have to go through filtering process and lots of machines dealing it and then isolating it making it likely not as potent!? but i could be wrong, who knows.

 

here is more information; https://www.ncbi.nlm...les/PMC3065441/ " Palm oil is one of the most abundant natural sources of tocotrienols, with crude palm oil (also referred to as the “tocotrienol-rich fraction”) containing up to 800 mg/kg weight of α- and γ-tocotrienol isotypes. The distribution of vitamin E in palm oil is 30% tocopherols and 70% tocotrienols."

Edited by sedentary, 21 October 2019 - 02:01 AM.

[sedentary]

repost

Edited by sedentary, 21 October 2019 - 02:02 AM.

[sedentary]

senolytic treatment (when high doses and many senolytics are combined) is best on weekends when you can rest

not when there s an illness or a surgery planned
 

 

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??