47 replies to this topic

[geo12the]

FYI new relevant study:

 

J Gerontol A Biol Sci Med Sci. 2016 Apr 18. pii: glw064. [Epub ahead of print]

Intermittent Administration of Rapamycin Extends the Life Span of Female C57BL/6J Mice.

Arriola Apelo SI1, Pumper CP1, Baar EL1, Cummings NE2, Lamming DW3.

Author information

• 1Department of Medicine, University of Wisconsin-Madison. William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin.
• 2Department of Medicine, University of Wisconsin-Madison. William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin. Endocrinology and Reproductive Physiology Graduate Training Program, University of Wisconsin-Madison.
• 3Department of Medicine, University of Wisconsin-Madison. William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin. Endocrinology and Reproductive Physiology Graduate Training Program, University of Wisconsin-Madison. dlamming@medicine.wisc.edu.

Abstract

Inhibition of the mTOR (mechanistic target of rapamycin) signaling pathway by the FDA-approved drug rapamycin promotes life span in numerous model organisms and delays age-related disease in mice. However, the utilization of rapamycin as a therapy for age-related diseases will likely prove challenging due to the serious metabolic and immunological side effects of rapamycin in humans. We recently identified an intermittent rapamycintreatment regimen-2mg/kg administered every 5 days-with a reduced impact on glucose homeostasis and the immune system as compared with chronic treatment; however, the ability of this regimen to extend life span has not been determined. Here, we report for the first time that an intermittent rapamycin treatment regimen starting as late as 20 months of age can extend the life span of female C57BL/6J mice. Our work demonstrates that the anti-aging potential of rapamycin is separable from many of its negative side effects and suggests that carefully designed dosing regimens may permit the safer use of rapamycin and its analogs for the treatment of age-related diseases in humans.

 

[Logjam]

To be fair to rapamycin, I see many more credible studies claiming life extension for rapamycin than c60oo -- by far.  That could change, and the credibility of c60oo is increasing, but I've been resisting the urge to let any of it in my body because nobody has a clue how it works.  I've heard it functions as an antioxidant.  I've heard it functions as an epigenetic regulator.  No thanks until I have an idea how it might work.

 

We do know how rapamycin works.  We know it has a few negative effects.  We don't know if c60oo has any negative effects except through lots of anecdotes here.

 

They're good anecdotes, but very few controlled studies as yet.  The most encouraging sign yet is this:

http://ichortherapeu...ology-research/, but still very little compared to rapamycin in the way of research.

 

I probably trust rapamycin in my body before I trust c60oo.  It's a "natural" macrolide produced by some bacterium, and I've let plenty of those in my body without event. c60 is far more alien to our cells.

Edited by Logjam, 21 April 2016 - 12:19 AM.

[adoado]

I started taking 1 mg every other day, also give to my mother, she is 80 i am 48, at 6 th pill, i had a sudden and severe backache, which disappeared within the night, my mom had diarrhea on 4th pill, which disappeared after one day, 

 

i considered myself lucky, if that will be all for side effects, but since our dosing is i presume, at the safe end, i do not expect anymore side effects other than adding 20 years to our lives.

 

i will take only 100 pills for around 200 days, and check my body then.

[Alpharius]

I would not take rapamycin each other day. The half life is too long. Intermittent dosage would be more something like 4-5 mg rapamycin each 10-14 days.

Edited by Alpharius, 15 April 2017 - 05:50 PM.

[adoado]

I would not take rapamycin each other day. The half life is too long. Intermittent dosage would be more something like 4-5 mg rapamycin each 10-14 days.

I know there are risks, but nobody can be sure of optimal dose, so we have to try and share the results.

[Alpharius]

The problem with EOD dosing 1 mg rapamycin is that you never really fully supress mTOR and you never really let it unsupressed. Maybe it works. But real intermittent dosage (in mice 1 time a week), had much less impact on metabolism and blood sugar and immune system, while it enhanced the life span. Chronic inhibition of mTOR1 results in mTOR2 inhibition too and this in insulin resistance. Switching mTOR off is ok but you need to switch it on from time to time.

[adoado]

The problem with EOD dosing 1 mg rapamycin is that you never really fully supress mTOR and you never really let it unsupressed. Maybe it works. But real intermittent dosage (in mice 1 time a week), had much less impact on metabolism and blood sugar and immune system, while it enhanced the life span. Chronic inhibition of mTOR1 results in mTOR2 inhibition too and this in insulin resistance. Switching mTOR off is ok but you need to switch it on from time to time.

are you taking? what should be the dosing?weekly 3-4 mg together one time?

[Alpharius]

Unfortunately I only once tried 4 mg a day, then I run out of my rapamycin and now I wait for new one. Before that I took 1 mg every day for a week together with metformin. But yes rapamycin has a very long half life of 60 hours. So if you take 4 mg today, in approximately 3 days you still have the 2 mg dosage equivalent in your blood, then after 6 days still 1 mg, and even after 10 days it is not 100% out of your system but low enough to let your mTOR be active again. 

I feel fine with rapamycin+metformin, mentally very clear. In the morning I feel somehow more fresh, maybe compareable to intermittent fasting.

 

I am not sure if 4 mg are the perfect solution, maybe 3 mg are enough or 5 mg are better, I have to check some more paper to find the exact mTOR supression dependent of dosage. I had found a paper about that but can not find it again. Patients who take Sirolimus for immune supression take on the first day 7 mg and then continue with 1 mg. 

 

Read this two paper:

 

https://www.ncbi.nlm...les/PMC4717280/

https://www.ncbi.nlm...pubmed/27091134

[adoado]

First paper is scary, they say even with intermittent dosing of 5 days, the testes weight was reduced by 60%, which is not acceptable if you are not a rat,

 

Why do you think we should switch mtor on and off???

Unfortunately I only once tried 4 mg a day, then I run out of my rapamycin and now I wait for new one. Before that I took 1 mg every day for a week together with metformin. But yes rapamycin has a very long half life of 60 hours. So if you take 4 mg today, in approximately 3 days you still have the 2 mg dosage equivalent in your blood, then after 6 days still 1 mg, and even after 10 days it is not 100% out of your system but low enough to let your mTOR be active again. 

I feel fine with rapamycin+metformin, mentally very clear. In the morning I feel somehow more fresh, maybe compareable to intermittent fasting.

 

I am not sure if 4 mg are the perfect solution, maybe 3 mg are enough or 5 mg are better, I have to check some more paper to find the exact mTOR supression dependent of dosage. I had found a paper about that but can not find it again. Patients who take Sirolimus for immune supression take on the first day 7 mg and then continue with 1 mg. 

 

Read this two paper:

 

https://www.ncbi.nlm...les/PMC4717280/

https://www.ncbi.nlm...pubmed/27091134

 

[Razor444]

I've been doing every other day (EoD) rapamycin. The only side effect I can detect is mouth ulcers (and not having to cut my nails as often). I also fast on days I don't take rapa--which inhibits mTOR, also. I spike mTOR around the time I weight train. Eat before training. Branch chain amino acids during training. Whey protein after training. I've been putting on a decent amount of muscle. Oh, and I also take red-hot baths, which I believe increases growth hormone.

 

I couldn't say how effective EoD is for lifespan/healthspan. It's been great for an autoimmune disease I've been struggling with, though (ulcerative colitis).

[Valijon]

Can anyone else elaborate on their experiences with rapamycin? Is anyone keeping a log? How much they take, how often they take it, how they feel, side effects, and additional supplements used in conjunction?

[PAMPAGUY]

The proper amount of rapa to take for aging.  Please read this entire web site by Dr. Alan Green who experimented on himself for the past 15 months with rapa + metformin + aspirin + Candesartan.  He is a board certified pathologist.  He knows what he is talking about.

 

https://rapamycintherapy.com/

[PAMPAGUY]

I started taking 1 mg every other day, also give to my mother, she is 80 i am 48, at 6 th pill, i had a sudden and severe backache, which disappeared within the night, my mom had diarrhea on 4th pill, which disappeared after one day, 

 

i considered myself lucky, if that will be all for side effects, but since our dosing is i presume, at the safe end, i do not expect anymore side effects other than adding 20 years to our lives.

 

i will take only 100 pills for around 200 days, and check my body then.

You want to give your mom 6 mg once a week + metformin.  That way the drug is out of her system before the next dose.  Every other day is no good. (good for transplant patients)  It continues to build up in system and causes bad side effects eventually.  At 48 yo, your too young to be doing aging intervention therapy.  You can improve with diet and exercise.  Your mom cannot.

 

https://rapamycintherapy.com/

[Nate-2004]

Aging begins pretty early so I would disagree with that part about 48 being too young. Early signs of aging begin around 30, so anyone over 30 may benefit. I am 42 and considering 6mg per week. I also diet and exercise and fasting, as many times as I keep trying it, I just can't do the extended fasts necessary to inhibit mTOR to the degree it needs to be. Metformin sounds like a good idea in conjunction. 

[PAMPAGUY]

6 mg a week is a dosage for full blown elderly people.  You might want to think this thru at that dosage.  3mg every other week would clear out your bad cells.  I take 1000 mg Metformin SR daily and that could be good to control your glucose especially if overweight.  Check the latest on the other blogs to keep up.  Taking NR would probably  do you more good and is a lot less expensive.  See this page

  

http://www.longecity...th-this/page-15

 

Good Luck,

 

 

[RWhigham]

See the Guarente video posted in BioScience by prophets

In old intestines, intestinal stem cells (ISCs) proliferate back to youthful levels if you raise NAD+ and SIRT1 and have mTORC1 functional. Inhibiting mTORC1 with rapamycin prevents this,  So I conclude, we should allow mTORC1 to fully recover between doses of rapamycin.  allowing our ISCs to benefit from boosting NAD+ and SIRT1. A similar effect may occur in other tissues.

 

Another interesting point in the video is that NAMPT decreases with age and is the upstream cause of NAD+ decreasing with age and of NAM increasing with age. Guarente talks about the excess NAM build up with age. Taking NAD+ precursors like NMN or NR bypass NAMPT to increase NAD+. It seems to me a better approach would be to restore NAMPT to youthful levels which would reduce NAM and restore NAD+ both to youthful levels. Guarente says the cause of NAMPT decline with age is currently unknown.

 

Guarente also points out that NAMPT has circadian cycle. Elsewhere one can find its mainly produced at night. I cannot locate it but I have seen a study where taking NAMPT "stimulators" in the morning reduces NAMPT, whereas taking them at night increases NAMPT.  So one should only take NAMPT stimulators like lithium and OPC grape seed extract at bedtime.

Edited by RWhigham, 17 August 2017 - 06:26 PM.

[Nate-2004]

I'm sure this is 6 of one half-dozen of the other but I wonder if you'd get different results taking 1mg every day for a week just 4 times a year (each season).

 

I'd like to get a group buy going but I don't know where the most legit place to source it from is.

Edited by Nate-2004, 17 August 2017 - 09:23 PM.

[PAMPAGUY]

Rapa removes scenence cells which are bad for you by inhibiting Tor 1.. Younger people don't have very many, but older have a lot.. Also we all need Tor 1 to live.. Just a matter of how much you inhibit Tor 1.. At 6 mg weekly, it is estimated at appx 65%.. Good Luck