955 replies to this topic

[geo12the]

Dasatinib sounds interesting but very expensive and where on earth do you get it from?

 

Relevant articles:

 

https://web.stanford...Brunet 2019.pdf

https://www.ncbi.nlm.../?report=reader

 

[judge]

WOW!  Great info!  Thanks!

[Valijon]

There was a group by some time ago on Dasatinib. I cant recall when it was. The thread should still be up. I'm sure that with enough interest, we could get another going again. So long as the guy who was in charge of it all is still around here somewhere.

[judge]

First 2 weeks I did 5 mg , now on my second week doing the grapefruit protocol with 3 mg . Read the medical information sheet that came with the rapamycin.  Says: because  grapefruit inhibits CYP3A4 it should not be used with or used for dilution of rapamycin.

 

Is this a concern?

 

Thanks!

[PAMPAGUY]

First 2 weeks I did 5 mg , now on my second week doing the grapefruit protocol with 3 mg . Read the medical information sheet that came with the rapamycin.  Says: because  grapefruit inhibits CYP3A4 it should not be used with or used for dilution of rapamycin.

 

Is this a concern?

 

Thanks!

judge, read my post #803.  Lots of info on grapefruit juice and rapa.

[judge]

judge, read my post #803.  Lots of info on grapefruit juice and rapa.

Thanks!  I re read the post and it is just a shame they way they lie on these supposed medical information sheets.  So when it says "grapefruit juice inhibits the CYP3A4-mediated metabolism of rapamycin."  That is a good thing, right?  

 

Also read fat is a big factor in absorption factor: it says: "absorbtion is affected by high fat meals"  But of course it does not say what the affect is!!!!

 

I am guessing from our knowledge that our digestive system readily absorbs fat that taking rapamycin with a high fat meal will increase absorption.  So that is a good thing?

 

Am I wrong????????

 

Would it affect the amount absorbed or the speed it is absorbed or both?    I am guessing both  lol

 

Thanks for the feedback!

[judge]

 2019 study shows DL001 analog of rapamycin to be many times more effective and not have side effects of regular rapamycin!

 

Here, we report the identification of DL001, a FKBP12-dependent rapamycin analog 40x more selective for mTORC1 than rapamycin. 

 

https://www.nature.c...467-019-11174-0

 

Hope this stuff comes out soon!

[Valijon]

Impressive, most Impressive. We must all get our hands on this and soon!

[aribadabar]

 2019 study shows DL001 analog of rapamycin to be many times more effective and not have side effects of regular rapamycin!

 

Here, we report the identification of DL001, a FKBP12-dependent rapamycin analog 40x more selective for mTORC1 than rapamycin. 

 

https://www.nature.c...467-019-11174-0

 

Hope this stuff comes out soon!

 

The link is bad.

 

Here is a good one to the paper: https://www.ncbi.nlm...les/PMC6642166/

[QuestforLife]

All that work and no lifespan study. I'll wait for that before I decide all the benefits definitely come from mTOR1 inhibition.

[PAMPAGUY]

One thing for sure, when they come out with rapalog it will cost as much as the brand names now.  Maybe insurance will cover it, but I wouldn't count on it.  There are now 2 anti-aging treatments, Tor inhibition and senolytics.   https://senolyticstreatment.com/

[judge]

The link is bad.

 

Here is a good one to the paper: https://www.ncbi.nlm...les/PMC6642166/

Thank you, I don't know why that link failed, hard to confirm since its abbreviated, thanks again!

[judge]

All that work and no lifespan study. I'll wait for that before I decide all the benefits definitely come from mTOR1 inhibition.

You might wan to go to the beggining of this thread and read all the hyperlinks,  hopefully you will be onvinced after that. 

It mostly started here:

 

In 2006, Mikhail Blagosklonny described how the mTOR pathway causedhyperfunction. In 2009 it was shown that rapamycin increased lifespan in mice by lowering the activity of the mTOR pathway.

[PAMPAGUY]

Here is Blagosklonny's latest paper.  The more rapa you take without side effects the longer and healthier life you will have.

 

 

 

https://www.ncbi.nlm...les/PMC6814615/

 

 

[judge]

Here is Blagosklonny's latest paper.  The more rapa you take without side effects the longer and healthier life you will have.

 

 

 

https://www.ncbi.nlm...les/PMC6814615/

That is the article that got me very interested in rapamycin, I saved it to my library, good info! Thanks!

[QuestforLife]

You might wan to go to the beggining of this thread and read all the hyperlinks, hopefully you will be onvinced after that.
It mostly started here:

In 2006, Mikhail Blagosklonny described how the mTOR pathway causedhyperfunction. In 2009 it was shown that rapamycin increased lifespan in mice by lowering the activity of the mTOR pathway.

Lol Judge

I started rapamycin in 2016. I've read tonnes of papers on it. A few people know more about rapamycin than me. You're not one of them.

[judge]

Yeah, I am a newbie, your post implied lack of knowledge, sorry.  Since you have been taking rapamycin, what benefits have you gotten from your protocol? Which protocol and what amounts are you doing now?

 

Thanks!

[QuestforLife]

Yeah, I am a newbie, your post implied lack of knowledge, sorry.  

 

Why because I questioned whether the life-extending benefits of rapamycin are definitely only due to mtor1 inhibition? That is the prevailing opinion and may well be correct, but it has not yet be definitively settled hence my wish to see a life-span study in any new rapalogs. There might also be a optimum mtor inhibition level and going below that might reduce lifespan (we don't know). 

 

Personally I think everolimus is a good bet once it comes down in price. It inhibits both mtor1&2 but its shorter half life (than rapamycin) means the effect on mtor2 would be reduced, permitting a larger dose and more profound mtor1 inhibition (again assuming that is what we want).

 

For the same reason I wouldn't use grapefruit juice, unlike many on this site - you'll get more rapamycin in your system for longer, but you'll end up with more side-effects (again possibly because mtor2 inhibition kicks in after sustained rapamycin serum concentration). Dr Alan Green agrees with me on this point. 

 

But the benefits and side effects of rapamycin seem to be heavily dependent on age. The older you are the greater the benefits:side effects ratio. Might be something to do with a greater senescent cell burden (which grows exponentially with age) and/or because the innate immune system gets so much stronger with age. There also seems to be quite a lot of individual variability in serum concentration of rapamycin when taking the same dose (woman have higher serum concentration, but i think this varies between members of the same sex too). So for this reason every individual needs to calibrate their own dose carefully. 

[Engadin]

...

 

But the benefits and side effects of rapamycin seem to be heavily dependent on age. The older you are the greater the benefits:side effects ratio. Might be something to do with a greater senescent cell burden (which grows exponentially with age) and/or because the innate immune system gets so much stronger with age. There also seems to be quite a lot of individual variability in serum concentration of rapamycin when taking the same dose (woman have higher serum concentration, but i think this varies between members of the same sex too). So for this reason every individual needs to calibrate their own dose carefully. 

 

 

It is a known fact that as we age, telomeres get shorter and shorter. And back in march, CNIO published a study that may shed some light on why as mice get older, rapamycin is increasingly less and less a friendly aging retardant, because they state that "the mTOR pathway is necessary for survival of mice with short telomeres". Should it work the same in elder humans, perhaps mTOR1 or 2 state should then be kept as intact as possible in our organism to slow down aging. Just my two cents.

Edited by Engadin, 01 June 2020 - 02:51 PM.

[Michael]

 the benefits and side effects of rapamycin seem to be heavily dependent on age. The older you are the greater the benefits:side effects ratio. Might be something to do with a greater senescent cell burden (which grows exponentially with age) and/or because the innate immune system gets so much stronger with age. There also seems to be quite a lot of individual variability in serum concentration of rapamycin when taking the same dose (woman have higher serum concentration, but i think this varies between members of the same sex too). So for this reason every individual needs to calibrate their own dose carefully. 

 

It is a known fact that as we age, telomeres get shorter and shorter. And back in march, CNIO published a study that may shed some light on why as mice get older, rapamycin is increasingly less and less a friendly aging retardant, because they state that "the mTOR pathway is necessary for survival of mice with short telomeres". Should it work the same in elder humans, perhaps mTOR1 or 2 state should then be kept as intact as possible in our organism to slow down aging. Just my two cents.

You have this backward: as QFL correctly notes, the benefit:risk ratio for rapa clearly improves as mice get older, not vice-versa. This is true for lifespan, for immunity, for muscles, and for multiple other parameters.

 

The so-called "mice with short telomeres"  in the Blasco (CNIO) study you reference are not normal, aging mice with short telomeres (telomeres don't actually shorten much in most aging tissues in humans or mice), but mice with genetic defects in their telomerase RNA template and then bred for multiple generations to further shorten their telomeres from before birth: they are in no way "old," and should not be taken as a model of aging.

Edited by Michael, 01 June 2020 - 04:29 PM.

[judge]

Why because I questioned whether the life-extending benefits of rapamycin are definitely only due to mtor1 inhibition? That is the prevailing opinion and may well be correct, but it has not yet be definitively settled hence my wish to see a life-span study in any new rapalogs. There might also be a optimum mtor inhibition level and going below that might reduce lifespan (we don't know). 

 

Personally I think everolimus is a good bet once it comes down in price. It inhibits both mtor1&2 but its shorter half life (than rapamycin) means the effect on mtor2 would be reduced, permitting a larger dose and more profound mtor1 inhibition (again assuming that is what we want).

 

For the same reason I wouldn't use grapefruit juice, unlike many on this site - you'll get more rapamycin in your system for longer, but you'll end up with more side-effects (again possibly because mtor2 inhibition kicks in after sustained rapamycin serum concentration). Dr Alan Green agrees with me on this point. 

 

But the benefits and side effects of rapamycin seem to be heavily dependent on age. The older you are the greater the benefits:side effects ratio. Might be something to do with a greater senescent cell burden (which grows exponentially with age) and/or because the innate immune system gets so much stronger with age. There also seems to be quite a lot of individual variability in serum concentration of rapamycin when taking the same dose (woman have higher serum concentration, but i think this varies between members of the same sex too). So for this reason every individual needs to calibrate their own dose carefully. 

Great info, thanks.  Got my curiosity up on rapalogs and found a decent article.  I had no idea so much study was put into cancer therapy. Sounds promising even though the studies were not conclusive, there were some good results.  I thought the grape juice just increased bio availability, did not read it would extend the half life?

https://cdrjournal.c...ticle/view/3277

[Engadin]

You have this backward: as QFL correctly notes, the benefit:risk ratio for rapa clearly improves as mice get older, not vice-versa. This is true for lifespan, for immunity, for muscles, and for multiple other parameters.

 

The so-called "mice with short telomeres"  in the Blasco (CNIO) study you reference are not normal, aging mice with short telomeres (telomeres don't actually shorten much in most aging tissues in humans or mice), but mice with genetic defects in their telomerase RNA template and then bred for multiple generations to further shorten their telomeres from before birth: they are in no way "old," and should not be taken as a model of aging.

 

Thanks Michael, I certainly missed QFL's point. For a total outsider like me lacking an ocean of knowledge, Mariana trench deep, terms and concepts, even though many times read about them, turn out blurred when attempting to reason one or two steps using them.

 

Thanks for the your patience and the clarity of your explanation, which I hope I won't missunderstand this time. LOL.

[Andey]

Why because I questioned whether the life-extending benefits of rapamycin are definitely only due to mtor1 inhibition? That is the prevailing opinion and may well be correct, but it has not yet be definitively settled hence my wish to see a life-span study in any new rapalogs. There might also be a optimum mtor inhibition level and going below that might reduce lifespan (we don't know). 

 

Personally I think everolimus is a good bet once it comes down in price. It inhibits both mtor1&2 but its shorter half life (than rapamycin) means the effect on mtor2 would be reduced, permitting a larger dose and more profound mtor1 inhibition (again assuming that is what we want).

 

For the same reason I wouldn't use grapefruit juice, unlike many on this site - you'll get more rapamycin in your system for longer, but you'll end up with more side-effects (again possibly because mtor2 inhibition kicks in after sustained rapamycin serum concentration). Dr Alan Green agrees with me on this point. 

 

But the benefits and side effects of rapamycin seem to be heavily dependent on age. The older you are the greater the benefits:side effects ratio. Might be something to do with a greater senescent cell burden (which grows exponentially with age) and/or because the innate immune system gets so much stronger with age. There also seems to be quite a lot of individual variability in serum concentration of rapamycin when taking the same dose (woman have higher serum concentration, but i think this varies between members of the same sex too). So for this reason every individual needs to calibrate their own dose carefully. 

 

  Do you have an opinion on cycling it on/off? 

I was forced to discontinue it due to a "limited supply due to recent events" and I would say I started to look a bit younger, gained some muscle even with decreased volume of exercise. Its possible that my stem cell pool was full for some time(thanks to Rapamycin) but wasnt used to a full extent because of rapamycin too. TBH I want to play with some periods on|off, esp as I  think @Turnbuckle protocol would benefit from such adjustment.

Edited by Andey, 02 June 2020 - 07:22 AM.

[PAMPAGUY]

  Do you have an opinion on cycling it on/off? 

I was forced to discontinue it due to a "limited supply due to recent events" and I would say I started to look a bit younger, gained some muscle even with decreased volume of exercise. Its possible that my stem cell pool was full for some time(thanks to Rapamycin) but wasnt used to a full extent because of rapamycin too. TBH I want to play with some periods on|off, esp as I  think @Turnbuckle protocol would benefit from such adjustment.

Andey, read my post #803.  Lots of info on grapefruit juice and rapa.  The Doctor mentioned there has himself, family members, and 50 patients on cycling rapa.  3 week cycles.  .18 mg/kg high to .07 mg/kg low.  Has years of experience, no substitute for that.  You can search for his name on the site and if I were you I would read everything he has to say.  Seems that chronic Tor inhibition (the chronic spike)  is where you get the most benefit in health and life span without side effects of course.  Large doses spaced further apart to prevent side effects.

[Andey]

Andey, read my post #803.  Lots of info on grapefruit juice and rapa.  The Doctor mentioned there has himself, family members, and 50 patients on cycling rapa.  3 week cycles.  .18 mg/kg high to .07 mg/kg low.  Has years of experience, no substitute for that.  You can search for his name on the site and if I were you I would read everything he has to say.  Seems that chronic Tor inhibition (the chronic spike)  is where you get the most benefit in health and life span without side effects of course.  Large doses spaced further apart to prevent side effects.

 

Thank you )

Can you elaborate a bit on 3 week cycles? as #803 doesnt mention it.  https://www.longecit...ndpost&p=892374

So far I ve taken everolimus for a about 2 years, as sublingual, I would probably add grapefruit a top of it to maybe drive it higher. I havent had any mouth sores anyway, so I dont expect it would be too much.

[PAMPAGUY]

Thank you )

Can you elaborate a bit on 3 week cycles? as #803 doesnt mention it.  https://www.longecit...ndpost&p=892374

So far I ve taken everolimus for a about 2 years, as sublingual, I would probably add grapefruit a top of it to maybe drive it higher. I havent had any mouth sores anyway, so I dont expect it would be too much.

I would suggest you search for Mark at the site and read all of his posts which are not that many, but very imformative.   https://forum.age-re.../rapamycin-cost

[InquilineKea]

https://www.slidesha...te-presentation - 5mg/week actually does show effects in some people

 

also can't one just use grapefruits rather than grapefruit juice to potentiate rapa?

Edited by InquilineKea, 04 June 2020 - 10:12 AM.

[judge]

https://www.slidesha...te-presentation - 5mg/week actually does show effects in some people

 

also can't one just use grapefruits rather than grapefruit juice to potentiate rapa?

My guess is it would work just as well, but you do absorb it faster in the form of juice.  Not sure if that affects absorption?  I squeeze 2 grapefruits night before and then squeeze 2 more grapefruit 30 minutes before dosing

[MikeDC]

Calorie restriction is more effective than Rapamycin

https://lifeboat.com...aximal-lifespan

[Engadin]

.

 

 

 

Transcription of a Carl Lanora interview to Dr. Mikhail Blagosklonny on 'Rapamycin As A Longevity Drug'.

 

 

 

S O U R C E  :   SuperHumanRadio

 

 

 

[00:00:00] Carl Lanore: [00:00:00] hey, welcome back to superhuman radio.  you know, we always find new Innovations in the ability to. Increase longevity in humans and we're always searching for this. Obviously. It's been around forever. I mean, we're always going to try to cheat death to some degree. It's our objective to live longer live happier lives.

[00:00:22] And so every now and then I come across a study or some work that has some promise and that's what today's show is about. My guest today is dr. Mikhail blackest Coney, but we're going to refer to you as Misha, right?

[00:00:35] Dr. Mikhail Blagosklonny: [00:00:35] All right,

[00:00:36] Carl Lanore: [00:00:36] okay, and we're going to be talking about. Something called rapamycin we've actually talked about it on the show in the past, but we're going to talk about it today in a slightly different context.

[00:00:46] So first of all for my listeners, we should explain what rapamycin is.

[00:00:51] Dr. Mikhail Blagosklonny: [00:00:51] Actually a prescription drug, which is used to prevent organ rejection after organ [00:01:00] transplantation. And it's also now used it's an Alex is anti-cancer drugs. So this is all drug. It was discovered long ago. But only recently something amazing actually happened with realized that this is a drug that suppresses each and agent from warm and flies right my mouth,

[00:01:31] Carl Lanore: [00:01:31] right?

[00:01:31] It starts out with the the elegant assists. What is it called the the worm that they worked with originally?

[00:01:37] Dr. Mikhail Blagosklonny: [00:01:37] Yeah c elegans. Yeah

[00:01:39] Carl Lanore: [00:01:39] c elegans. Yeah. Now it's important to understand something rapamycin was. Discovered as a as a bacteria, correct on the Easter Island of Rapa Nui, and hence. That's where the name rapamycin came, right?

[00:01:52] And and right now it's manufactured by Wyeth under the name rap immune which is is used for as you pointed out individuals who [00:02:00] undergo organ transplant. They give them this medication so that their body doesn't reject the organ. So it's suppressor which suppresses the immune system correctly?

[00:02:09] Dr. Mikhail Blagosklonny: [00:02:09] Well, we're studying this right now.

[00:02:13] I would call it. It's it rejuvenate immune system because in Old mice it was shown that it's actually stimulating monitor. So. It's not such harsh immunosuppressant. So maybe it maybe

[00:02:32] Carl Lanore: [00:02:32] it almost has

[00:02:35] Dr. Mikhail Blagosklonny: [00:02:35] an adapted genic side to it then right and besides that in we think that in the right Doses and right formulations, it could be used without any immunosuppression.

[00:02:48] So at least mice live longer when they take rapamycin and. Their formation to lease cancer and humans [00:03:00] who are taking report mice and because of organ rejection, they have some side effects, but one of these side effect is that there is less cancer interesting interesting. So with such positive side effect.

[00:03:17] Carl Lanore: [00:03:17] Okay. Now there's lots of research into into chemoprevention. And and cancer drugs out there some of them work to re-establish cellular apoptosis While others seem to affect inflammation and the inflammatory response by the immune system. It sounds like wrapper myosin works. Through the ladder pathway.

[00:03:39] Am I correct in assuming

[00:03:41] Dr. Mikhail Blagosklonny: [00:03:41] that? Yes traditionally. It was taught the tropomyosin will directly kill cancer cells, but this is very non toxic drug and. In my opinion mechanism of chemo prevention that slows down organismal [00:04:00] aging. So this is beautiful situation and we may prevent cancer by staying here on because each agent is the major risk factor of cancer.

[00:04:14] Carl Lanore: [00:04:14] Right, you know what? I just thought of it just dawned on me to have you looked at the effects of rapamycin on the telomere.

[00:04:26] Dr. Mikhail Blagosklonny: [00:04:26] Well, we didn't we didn't

[00:04:29] Carl Lanore: [00:04:29] it would be interesting to see where I'm going with that right? You would be interesting because we know that as the telomere becomes shorter the probability of a mutant replication of that DNA becomes more prevalent and a lot of and there is some.

[00:04:43] Evidence that that could lead to certain types of cancers

[00:04:46] Dr. Mikhail Blagosklonny: [00:04:46] beautiful hips but one of the major mechanism of slowing down organismal agent because another treatment that [00:05:00] prolong life span calorie restriction, it deletes cancer in my soul my sleep longer and can see it you late because. Really hsf it disease especially prostate breast colon and so on my so if we slow down our region we can delay can soap he wanted and and in the same.

[00:05:30] We can prevent or delay other issues related diseases

[00:05:34] Carl Lanore: [00:05:34] right now. We're going and we're going to talk more about the different diseases that actually this is that its effects but let's just stay just for a moment longer on the longevity Effectiveness. As you mentioned a moment ago. There seems to be a relationship between rapamycin and hypochlorous very very Ultra low-calorie diets.

[00:05:50] We already know at least we thought we knew the mechanism that that hypochlorite diets work through by increasing search ruins. Is there a relationship between. [00:06:00] Search ruins and the mammalian Target of rapamycin.

[00:06:04] Dr. Mikhail Blagosklonny: [00:06:04] Well, actually I have a little bit different point of view. How can I make you some of calorie restriction?

[00:06:13] What is another name of Target of rapamycin Toro mtor its nutrient sensing pathway. So what nutrients are doing glucose proteins amino acids this stimulate tour and we stimulate and tour they accelerate aging. So when we live or my Sleepless we animals tour is the activate slightly but rapamycin deactivated strongly.

[00:06:45] So in this it could be much more potent life-extension treatment that calorie restriction and besides it actually it was shown that it's probably will less appetite. [00:07:00] So people will even. Cliff and losing some weight and at the same time it it might be much more benign treatment in calorie restriction

[00:07:12] Carl Lanore: [00:07:12] interesting.

[00:07:13] And you know, when you talk about tour the target target of rapamycin, I'm trying to Envision. What tour is. Is this a receptor?

[00:07:24] Dr. Mikhail Blagosklonny: [00:07:24] Well if it's intersil. Protein signal transduction pathway and this is relatively low in Signal transduction pathway, but why I am talking about Tour all the time because it stands out because we have clinically available drug to inhibit it

[00:07:45] Carl Lanore: [00:07:45] right.

[00:07:48] And I didn't mean to cut you off. I'm just agreeing with you. I'm sorry.

[00:07:50] Dr. Mikhail Blagosklonny: [00:07:50] Yeah, so if you said correctly it was discovered. It is product which produced by bacteria and [00:08:00] bacteria produce it to inhibit growth of East. So it's something opposite to mirror image of binitarianism. So by in the growth is drink to it.

[00:08:16] Because when we stop growing with start aging so Torres involved at the beginning in growth and then an agent for that reason republicanism produced by bacteria inhibit growth of East but also inhibit their agent interesting now, there

[00:08:35] Carl Lanore: [00:08:35] is a drug on the market called a finit or which is an is an mtor.

[00:08:42] Inhibitor does that have the same effect as taking rapamycin by by inhibiting empty the the mammalian Target of rapamycin is that it does have the same effect.

[00:08:53] Dr. Mikhail Blagosklonny: [00:08:53] Well, there are several Inhibitors of mtor. Okay, [00:09:00] and some of them are not look so for the permits and those that analysis of rapamycin and they used mostly for cancer treatment.

[00:09:10] They have the same effect, but some drugs probably. Have a little bit different effects one Interesting Drug by the way is not for mean. This is well-known drug, which is used diabetes for diabetes.

[00:09:29] Carl Lanore: [00:09:29] It's actually the gold stamp metformin is the gold standard for diabetes treatment nowadays,

[00:09:33] Dr. Mikhail Blagosklonny: [00:09:33] right?

[00:09:33] And it's used for type 2 diabetes and. It was shown recently that it's also slightly increased lifespan and mice and increase insulin sensitivity and other benefits benefits, but recently turned out that this is indirect inhibitor [00:10:00] of

[00:10:00] Carl Lanore: [00:10:00] M2

[00:10:04] Dr. Mikhail Blagosklonny: [00:10:04] are in direct indirect and direct.

[00:10:05] Carl Lanore: [00:10:05] Okay. Let's take a quick commercial break.

[00:10:07] And when we come back, we're going to continue this conversation going to delve more into the potential longevity. Effects of rapamycin my guest today is Mikhail Vlados Coney. He likes me to call a Misha. Thank you for that because it's a lot easier stay tuned. We'll

[00:10:23] Dr. Mikhail Blagosklonny: [00:10:23] be right back want to

[00:10:26] Carl Lanore: [00:10:26] remind everybody that orbit nutrition is having a special supremum radio, listener 10% discount off their already low prices.

[00:10:39] At checkout use the coupon code shr 10, that's sa sh. 1 0 visit orbit nutrition.com. 

[00:10:45] Dr. Mikhail Blagosklonny: [00:10:45] my

[00:10:48] Carl Lanore: [00:10:48] guest today is dr. Micha blackest coning. We're talking about rapamycin its effect on longevity.

[00:10:58] Make sure did you want to say [00:11:00] something before we went into the break? Did you want to finish her statement from?

[00:11:03] Dr. Mikhail Blagosklonny: [00:11:03] Are actually I am ready to continue. Yes. I have a lot of interested.

[00:11:11] Carl Lanore: [00:11:11] Okay. Let me ask you a question. One of the unique things about rapamycin was that it was as effective on older.

[00:11:19] Subjects in these studies mice for instance it even extended life in mice that were the equivalent of 60 years old and Youmans and human age, correct? I mean, so it was something that even though it was introduced later in life it still extended. All

[00:11:32] Dr. Mikhail Blagosklonny: [00:11:32] right, right, right. And actually this was predictable.

[00:11:38] I wrote about this in some my theoretical papers even four years ago. So basically if my son inhibits agent it delays each related diseases so it delays [00:12:00] causes of death. So it doesn't really treat diseases but delays, for example, if somebody has osteoporosis, which is H related disease, right? In this case by inhibiting agent we can delay was to paralysis.

[00:12:22] Carl Lanore: [00:12:22] So basically what you're really doing is you're not slowing down the clock.

[00:12:26] Dr. Mikhail Blagosklonny: [00:12:26] Yeah the clock but if person with osteoporosis have a broken Heap in this case, but my son will not help

[00:12:35] Carl Lanore: [00:12:35] a little slow the healing down.

[00:12:37] Dr. Mikhail Blagosklonny: [00:12:37] Yeah, right. So the same with everything else, for example, it can delay the progression of atherosclerosis, but if stroke average a occurs, for example, it cannot repair, you know,

[00:12:54] Carl Lanore: [00:12:54] you know what I find interesting and I look at I I did a show last year [00:13:00] with a I want and I tried to dig this up during the break and I couldn't find it fast.

[00:13:04] But I did a show last year. I interviewed a scientist from Canada. I believe he was in Quebec and they had published a study up there. Then it was glucose signaling that lead to Advanced aging and they had done these these studies and yeast and then in C along Al guante and then they were doing them in mice and it was glucose signaling and at the thing I find interesting is that.

[00:13:30] One of the one of the natural natural supplements that is supposed to also have an effect on longevity and health is is Resveratrol its ability to up reg search you as well. The interesting thing about Resveratrol is what Resveratrol was found to be as effective on a milligram per milligram basis as metformin.

[00:13:54] And managing blood glucose. So when you said that about metformin a moment ago, and you said you know that has the [00:14:00] ability to also have some of these effects and indirectly lower mtor and I and all of a sudden I thought well, maybe that's all you know what we're learning here. I think more than anything else you got it's not there's no one thing it's actually an orchestrated thing group of things that have to happen

[00:14:17] Dr. Mikhail Blagosklonny: [00:14:17] isn't.

[00:14:18] Right, but it did it for a million and Resveratrol they in directly inhibit tour M2. Are you die? Yes, I'll withhold this and some other scientist also publish this data that Resveratrol and high dose. Inhibits interactivity but indirectly, so when I am talking about Target of Resveratrol I say indirectly mtor is very thorough.

[00:14:52] Okay? Okay

[00:14:54] Carl Lanore: [00:14:54] now so now so now the the the the rapper myosin extended life the equivalent of [00:15:00] 30 percent.

[00:15:02] Dr. Mikhail Blagosklonny: [00:15:02] Well, actually it was one study and the permits and was started late in life. So it would be interesting to see if it started in middle life. It should not be started. Of course in young in America growing, right?

[00:15:23] Yes. This is pure second. It's not clear what formulations and doses should be used. It's not clear how it should be combined with diet. We're working on this important questions because. We need to develop Rapport myosin, which is not even surprised if at all right at Sajid Doses and formulations, or you can combinations with some other drugs for example with it for me.

[00:15:55] And so there is a lot of possibilities [00:16:00] but. What is important about repair my son did unlike other investigational drugs? It's inhuman used for many years

[00:16:11] Carl Lanore: [00:16:11] well, and and and and and because it's a was actually used for a while as an antifungal before it was used as a chemo protective, right?

[00:16:18] Dr. Mikhail Blagosklonny: [00:16:18] Right and besides it.

[00:16:21] It was many style studies that information was started for almost every year existing age related disease and this study were done by experts in different fields. And when I collect together all these data is become clear that the reason why rapamycin could be used for atherosclerosis Parkinson's disease for example,

[00:16:54] Carl Lanore: [00:16:54] and also Harbors disease to they're having success with it, right?

[00:16:57] Dr. Mikhail Blagosklonny: [00:16:57] Well this animal [00:17:00] models in animal models,

[00:17:04] Carl Lanore: [00:17:04] right? That's right, right.

[00:17:05] Dr. Mikhail Blagosklonny: [00:17:05] Yeah, so in this animal models, so why one drug? Could be used for such different applications and then say is that mechanism of action is slowing down inhibiting agent. So all aging age-related diseases have a common component which is inhibited by this one single drug.

[00:17:31] That's

[00:17:32] Carl Lanore: [00:17:32] it's amazing. Yes. I mean a real, you know. I mean, we're always looking for and even pharmaceutical companies are always looking for a single drug that has multiple benefits, but rapamycin really really does seem to be that.

[00:17:48] Dr. Mikhail Blagosklonny: [00:17:48] Right. This is what I probably just and including how we can use it for example for treatment and prevention [00:18:00] advantages and then in the same patients to try to observe its effect on other disease because then all the people several diseases usually coexist right could be high blood pressure if it could be diabetes.

[00:18:16] Obesity and macular degeneration and so on by the way, it was very interesting story about macular degeneration

[00:18:28] Carl Lanore: [00:18:28] of the diatom of the ocular disease macular

[00:18:32] Dr. Mikhail Blagosklonny: [00:18:32] degeneration. Okay. Okay. This is a few major cause of blindness and there is no very effective treatment. And when five years ago, I realized that rapamycin is actually engage in drug for humans.

[00:18:54] In this case. It should slow down all diseases. [00:19:00] So I. Wait mental experiment. I choose 1 TC is which I was not familiar. It was macular degeneration. And and I went to after Mall adjust. My good friend asked did he hear about the parmesan because I thought he would say yes, and it was not no one but.

[00:19:25] After one year, I want it very successful company started developing for my son in California for treatment of macular degeneration. Really? Yes, they started doing this for different professionals. They worked on this for many years before. So it was not my influence of course, but but they found this coincidence that theory work.

[00:19:54] So it does it does

[00:19:58] Carl Lanore: [00:19:58] work that does it [00:20:00] does it just slow the progression of the disease or does it reverse

[00:20:03] Dr. Mikhail Blagosklonny: [00:20:03] it? Well, I quote information only from website of this company, so. It was not complete disclosure. Okay.

[00:20:19] Carl Lanore: [00:20:19] Now we're going to take a break in just a moment. But if we could just address one other thing that I have a special interest in you said that wrapper myosin seem to benefit.

[00:20:27] Those who suffer from Parkinson's disease. Once again, does it just slow the progression of the disease or can actually keep the disease at Bay and definitely

[00:20:35] Dr. Mikhail Blagosklonny: [00:20:35] well if we're talking a lot about humans, but about animal models, right and in animal models these diseases slow slightly different, but basically what repair my son is doing is decrease synthesis of this abnormal proteins and increase.

[00:20:55] Sales each and still can eat this abnormal proteins if [00:21:00] you decrease over activation of cell, so because Phil overactivation conventionally cause damage gotcha. All right, let's

[00:21:11] Carl Lanore: [00:21:11] do this. Let's take a quick commercial break and when we come back, I've got some more questions for you. We're talking about rapamycin today.

[00:21:19] And its ability to lengthen life stay tuned. We'll be right back. Hey, this is Carl before teen years. You've heard me talk about can see eye drops and they being the reason that I do not need reading glasses at now 61 years old, but I regularly get emails and messages from people who've been using can see and having some amazing results.

[00:21:40] Recently, I got an email from a fellow named Chad who because he was on dexamethasone eye drops for over six months developed a cataract can see eye drops actually reduced my cataract to the point where even my doctor has a hard time finding it. I will never stop using can see eye drops twice a day.

[00:21:56] I've been using them since 2008 he says and you should be [00:22:00] too there is no better way. To keep your eyes healthy and seeing clearly then can see eye drops go to Wise Choice medicine.com today and get on board and we will both be looking into the future with very clear Vision.

[00:22:16] Dr. Mikhail Blagosklonny: [00:22:16] It's

[00:22:16] Carl Lanore: [00:22:16] superhuman

[00:22:18] Dr. Mikhail Blagosklonny: [00:22:18] radio.

[00:22:21] Carl Lanore: [00:22:21] Welcome back to super human radio.  My guest today is dr. Mikhail like a Stony we're talking about rapper myosin and its. On longevity.  I just want to mention something. There is a banner ad on supremum radio.com for GLC. Mm buy one get one free and you really have to call their phone number their toll-free 800 number if you click the link that's on the website and once you go to their website call the 800 number and tell them you are a listener of superhuman radio and they will it's an outstanding.

[00:22:58] GLC mm is already [00:23:00] the least expensive highest potency glucosamine chondroitin product on the market and getting a buy one get one free is like getting it for half price. So it's out stands to check them out GLC direct.com.  Make sure the obviously the big concern and you mentioned that the the role now is to find rapamycin that does not inhibit.

[00:23:23] Immune function obviously, but what if what if part of the benefits of rapamycin are because it does inhibit immune function what if some of the aging process is actually self-imposed so to speak a process that the immune system over time starts to maybe attack the body.

[00:23:46] Dr. Mikhail Blagosklonny: [00:23:46] All right, actually, this is really good put that you just said because people don't realize this that each gene is associated with autoimmune diseases [00:24:00] and increase immunity and something hyper immunity and inflammation in general also is associated with aging so.

[00:24:11] If I would say different way to look at this report, my son is labeled is immunosuppressant because it's it it is sold for this purpose. It could be labeled anti-cancer drug contagion or anti-inflammatory for example, like aspirin, right? So in this case if it would be called until. I told you we would not be worrying.

[00:24:44] Carl Lanore: [00:24:44] When what we wouldn't worry about its immunosuppressive agents because it's worth focusing on something else,

[00:24:51] Dr. Mikhail Blagosklonny: [00:24:51] right so that have waited different immunosuppressants and rapamycin is very [00:25:00] benign. I would say but what is important is to develop? And formulations that it will be lower Doses and so on which would exclude any side effects because rapamycin would developed specifically for those Ascent schedules specifically for transplant patients for as anti-rejection drug.

[00:25:37] No,

[00:25:38] Carl Lanore: [00:25:38] I'm sorry. No, go ahead.

[00:25:39] Dr. Mikhail Blagosklonny: [00:25:39] Now we need to redevelop with and actually we're gonna sit spin off with Russell Parker company 30th, which is now working on this to develop Rapport. Meissen is anti-aging drug.  [00:26:00] Are

[00:26:00] Carl Lanore: [00:26:00] you seeing resistance about I mean? I realized that more and more people in medicine are starting to get the idea that those of us who have been on the front end of anti-aging.

[00:26:10] It's not about finding a younger wife and and looking young. It's about staving off age-related disease and I think that the term anti-aging is almost become whitewashed with zealots who would Infuse their bodies with dangerous things just to look younger. And are you a do you see any difficulty when you start talking about rapamycin as an anti-aging agent.

[00:26:39] Do you have your key your colleagues? Look at you like oh, you know Ponce de Leon. Here we go.

[00:26:45] Dr. Mikhail Blagosklonny: [00:26:45] All right, and also there is not the problem here most scientists who work in ijen. They not familiar with clinical use of rapamycin. So at [00:27:00] first especially many years ago when I was talking about that the action from basic scientist was that but you cannot use for my season in humans.

[00:27:11] If voice and we use it in the laboratory and I was saying but it's already used in humans. So then the sea but at first you need to check the affected mice at least I said it was all done 30 years ago. So it was developed and approved by if d e by in almost all countries. So now we just need to take advantage and amazing and that that if many people are ready take in Reformation, we can study this patients for something else.

[00:27:57] For example. [00:28:00] One cancer prevention. One said it's clear which is by the way. The information is also used on coronary stents on

[00:28:13] Carl Lanore: [00:28:13] what carotid stents

[00:28:15] Dr. Mikhail Blagosklonny: [00:28:15] you said coronary stents its stance. Which completed.

[00:28:21] Carl Lanore: [00:28:21] Oh, yeah, coronary stents. Yeah because they are right now they use what was the I know talking about okay and and Plavix they have the Plavix tint and so on and so.

[00:28:29] Um, yeah, so

[00:28:31] Dr. Mikhail Blagosklonny: [00:28:31] so to prevent restenosis of Artesia, so it was another study and which stands was used without permission but repair my son was taking Perros or earlier, right? And it also helped to prevent these Technologies. So it means that my son actually mm reduce. Griffin and humans [00:29:00] it was shown in mice that it's delete to the sclerosis in my special genetic mites, which have it very fast.

[00:29:14] So another very interesting side effect, which is observed in it. Almost it almost seems

[00:29:23] Carl Lanore: [00:29:23] like rap a myosin. Yeah, does the correct everything that is wrong with our societies the way of eating and living it's almost it's you know, it reduces inflammation. It slows down aging and as a result of slowing down aging it has a profound effect on.

[00:29:46] A myriad of diseases.

 

 

 

 

 

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