Rapamycin prevents age-related brain vascular deterioration in rats

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BrianR
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Rapamycin prevents age-related brain vascular deterioration in rats

Postby BrianR » Thu Nov 07, 2019 3:58 pm

ScienceDaily summary: https://www.sciencedaily.com/releases/2019/11/191106162529.htm
In the study, published Nov. 6 in the journal Aging Cell, researchers began rats on a diet including low-dose rapamycin at 19 months old (past middle age in rat years). Rapamycin treatment in daily food continued until the mice were of advanced age -- 34 months old -- almost double the age they were when they started treatment. "Essentially this is as old as these rats can get. These animals were very old but still, blood circulation in the brain was exactly the same as when they started treatment," said study senior author Veronica Galvan

For those of you who like the hard stuff, here's the actual [open access] paper:

mTOR drives cerebrovascular, synaptic, and cognitive dysfunction in normative aging
https://onlinelibrary.wiley.com/doi/full/10.1111/acel.13057
Candice E. Van Skike, Ai‐Ling Lin, Raquel Roberts Burbank, Jonathan J. Halloran, Stephen F. Hernandez, James Cuvillier, Vanessa Y. Soto, Stacy A. Hussong, Jordan B. Jahrling, Martin A. Javors, Matthew J. Hart, Kathleen E. Fischer, Steven N. Austad, Veronica Galvan.
Aging Cell, 2019; DOI: 10.1111/acel.13057


Obligatory disclaimer: Rats and humans differ.

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Re: Rapamycin prevents age-related brain vascular deterioration in rats

Postby Kenny4/4 » Thu Nov 07, 2019 7:08 pm

Rapa and mTOR the master keys to the castle of aging. Unfortunately unless I get an organ transplant the medical world won’t be handing me out any Rapamycin. I guess it’s IF, calorie and protein restriction/management, Resvertrol,NMN and grape seed extract to hack mTOR.

Great info in the report as it confirms some of my Recent microvascular musings-worries and illustrates how well Rapamycin can stave that off.
Does anyone know what the all cause mortality curve is on Rapamycin compared to say standard life insurance mortality curves?
Thanks for the report Brian!

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Re: Rapamycin prevents age-related brain vascular deterioration in rats

Postby SusanJ » Fri Nov 08, 2019 4:56 am

Kenny4/4 wrote:Rapa and mTOR the master keys to the castle of aging. Unfortunately unless I get an organ transplant the medical world won’t be handing me out any Rapamycin.


Definitely a better approach to use the things you listed. Here is a 2019 study that cautions that rapamycin can't be used long term anyway.

Long-term inhibition of mTOR by rapamycin or latrepirdine also prevents AD-like cognitive deficits and lowers Aβ42 level, reduces amyloid plaques and tau NFTs (McGowan et al., 2005; Caccamo et al., 2010; Spilman et al., 2010; Majumder et al., 2011). Yet it is noteworthy that the mTOR pathway itself is involved in many other critical cellular functions such as gene translation and cell growth. Toxic side-effects on patients can be induced by long-term inhibition of the mTOR pathway. So, rapamycin is not an ideal drug candidate to be considered for long-term use. Novel specific autophagy inducer is urgently needed for the field.


https://www.frontiersin.org/articles/10 ... 00203/full

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Re: Rapamycin prevents age-related brain vascular deterioration in rats

Postby Tincup » Fri Nov 08, 2019 5:34 am

Kenny4/4 wrote:Unfortunately unless I get an organ transplant the medical world won’t be handing me out any Rapamycin!


Allan Green MD, who has posted here as alangreenmd (you can search on this as the poster) has a practice prescribing off label use of rapamycin for aging. https://alzheimer-prevention.com/introduction
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Re: Rapamycin prevents age-related brain vascular deterioration in rats

Postby Kenny4/4 » Fri Nov 08, 2019 4:29 pm

Tincup wrote:
Kenny4/4 wrote:Unfortunately unless I get an organ transplant the medical world won’t be handing me out any Rapamycin!


Allan Green MD, who has posted here as alangreenmd (you can search on this as the poster) has a practice prescribing off label use of rapamycin for aging. https://alzheimer-prevention.com/introduction
Thanks for the info everyone, Much appreciated. I’ll continue au naturale with my prevention strategies. mTOR does explain a lot of the lower protein society /CR-longevity connection.

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Re: Rapamycin prevents age-related brain vascular deterioration in rats

Postby Newtothis3/4 » Wed Nov 13, 2019 3:13 pm

I have been using Rapamycin now for about 6 months for AD prevention and longevity. I have been very pleased so far with the results.

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Re: Rapamycin prevents age-related brain vascular deterioration in rats

Postby BrianR » Wed Nov 13, 2019 4:08 pm

Newtothis3/4 wrote:I have been using Rapamycin now for about 6 months for AD prevention and longevity. I have been very pleased so far with the results.

This is very interesting Newtothis3/4. What improvements have you measured? Any unpleasant side effects? If you don't mind, what's your dosage?

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Re: Rapamycin prevents age-related brain vascular deterioration in rats

Postby Newtothis3/4 » Wed Nov 13, 2019 5:24 pm

Dosage is 5-6mg once a week.
My data is completely subjective. With my understanding of intermittent Rapa for longevity and the many Rapa animal studies that have been done so far, I have some signs it is working (in terms of side effects).
My insulin level has not really changed. Lipids went up from 145 to 200. Increased Crestor from 5mg every other day to every day and TC went back to 145 with low triglycerides (same as before).
I feel like my immune system is much better. Totally subjective, maybe placebo but after this many months most likely a result of improved immunity. Studies have shown Rapa increases the flu vaccine efficacy by 40%. I also had allergies before Rapa and since I’ve started Rapa, they are gone. Wound healing seems a bit slowed which is to be expected. I don’t have huge cuts or lacerations, but a scratch seems to take about twice as long to heal. I use medical marijuana and have always had problems with how some strains made me anxious, etc. So much, that I could only use one type. With Rapa, I can use any strain, as much as I want, and only feel the relaxing and therapeutic effects. The study Dissociation of the Pharmacological Effects of THC by mTOR Blockade shows “Therefore, mTOR inhibition by temsirolimus allows the segregation of the potentially beneficial effects of cannabinoid agonists, such as the anxiolytic and antinociceptive effects, from the negative effects, such as anxiogenic- and amnesic-like responses.” Meaning, the mice got high, still got the pain relief and didn’t get any anxiety or short-term memory loss from marijuana and Rapa combo. I must be like the mice because my experience has been the very same.
My body composition seems to be changing a bit more as well. I am in very good shape, but the very last fat left on my abdomen has been going away without any other change in diet or excercise. That never has happened and I speculate it is a result of my body being in autophagy.
So, all my observations are subjective. The anti-cancer and AD prevention benefits are taking place at the cellular level, 24/7. They are occurring as evidenced by the observations I’ve seen which support the notion my Mtor1 is down and I am in autophagy.

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Re: Rapamycin prevents age-related brain vascular deterioration in rats

Postby Newtothis3/4 » Wed Nov 13, 2019 6:37 pm

SusanJ wrote:
Kenny4/4 wrote:Rapa and mTOR the master keys to the castle of aging. Unfortunately unless I get an organ transplant the medical world won’t be handing me out any Rapamycin.


Definitely a better approach to use the things you listed. Here is a 2019 study that cautions that rapamycin can't be used long term anyway.

Long-term inhibition of mTOR by rapamycin or latrepirdine also prevents AD-like cognitive deficits and lowers Aβ42 level, reduces amyloid plaques and tau NFTs (McGowan et al., 2005; Caccamo et al., 2010; Spilman et al., 2010; Majumder et al., 2011). Yet it is noteworthy that the mTOR pathway itself is involved in many other critical cellular functions such as gene translation and cell growth. Toxic side-effects on patients can be induced by long-term inhibition of the mTOR pathway. So, rapamycin is not an ideal drug candidate to be considered for long-term use. Novel specific autophagy inducer is urgently needed for the field.


https://www.frontiersin.org/articles/10 ... 00203/full


Intermittent Rapa does not cause any of the side effects known with daily dosing of Rapa. The reason is that daily dosing is required to keep a trough level high enough to cause both Mtor1 AND Mtor2 to go down. With intermittent, only Mtor1 goes down and leaves Mtor2 untouched.


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