20 replies to this topic

[MikeDC]

A recent study confirmed again that both NMN and NR depends on NRK1 and NRK2. This means that NMN is converted to NR first before entering the cells.

NAD+ up regulate sirt1 which down regulate mTORC1. So increasing NAD+ can also take care of Rapamycin action. Which makes Rapamycin unnecessary. It is a good thing since Rapamycin has many serious side effects. Consider NR and NMN as perfect mTORC1 inhibitors and much more.

[MikeDC]

Metformin by itself does not extend life span. It is used in combination with Rapamycin to reduce one of the side effects of Rapamycin which is insulin resistance.

[MikeDC]

Sirt1 regulate mTORC1 and AMPK.

https://www.ncbi.nlm...om=mtorc1 sirt1

Edited by MikeDC, 03 August 2017 - 07:54 PM.

[smithx]

So NMN is orally available, and they seem to be testing 500mg or 1g doses.

 

I think we looked into a group buy of NMN at some point and it was too expensive. Maybe worth revisiting. I see that RevGenetics is selling 25g of 99.3% pure NMN for $13.43 per gram . Not sure how much cheaper it may be available elsewhere.

 

The other question is whether NMN is really better to take than NR, especially in light of:

https://brenner.lab....Trammell16c.pdf

 

 

Edited by smithx, 03 August 2017 - 08:31 PM.

[MikeDC]

https://www.ncbi.nlm...namide riboside

[Rick Flair]

It is a good thing since Rapamycin has many serious side effects

This is false. At 6mg per week, no such serious side effect. You should go sell vitamins some where else.

[Rick Flair]

Metformin by itself does not extend life span. It is used in combination with Rapamycin to reduce one of the side effects of Rapamycin which is insulin resistance.

Dr. Green addresses this on his website. This is also false. Why do you want to bash Rapamycin so much?

[MikeDC]

Rapamycin helps to kill senescent cells. But NAD+ helps to prevent and rescue senescent cells. The mTORC1 inhibition is better handled by Sirt1. So the best approach is to use NAD+ precursor to rescue senescent cells first and use it long term to upregulate sirt1 and down regulate mtorc1. Rapamycin can be used for two weeks every year to kill senescent cells. Ignoring NAD+ precursor and only focus on Rapamycin is a big mistake you will regret eventually.

[Rick Flair]

More of your opinion. More Bashing. GO SELL VITAMINS SOMEWHERE ELSE.

[smithx]

Killing senescent cells is not at all the mechanism suggested for rapamycin's anti-aging effects.  This article may provide some useful information on what it is thought to be doing:

http://www.jci.org/articles/view/64099

 

 

Rapamycin helps to kill senescent cells. But NAD+ helps to prevent and rescue senescent cells. The mTORC1 inhibition is better handled by Sirt1. So the best approach is to use NAD+ precursor to rescue senescent cells first and use it long term to upregulate sirt1 and down regulate mtorc1. Rapamycin can be used for two weeks every year to kill senescent cells. Ignoring NAD+ precursor and only focus on Rapamycin is a big mistake you will regret eventually.

 

[maxwatt]

posts moved to here from Rapamycin thread

[mrkosh1]

First of all, it is absolutely clear to me that NMN must be converted to NR before it is able to pass through the cell membrane. This is a fact. There are papers that detail this including the thesis that I've posted on this forum before. If NMN could be produced in such a manner (modified in some way) so that it could pass through without first having to be converted to NR, then NMN would be clearly superior. 

 

Secondly, I'm really wondering if what we really need is alternating periods of suppression of mTORC in favor of autophagy and high levels of SIRT1 expression and other periods of explosive growth. My thinking would be like this....

 

1) Fast and take NR along with other supplements that could help induce autophagy and SIRT1 and PARP. Basically, you are killing and destroying senescent or cancerous cells.

 

2) Once a certain percentage of the "bad" cells (damaged, old, or cancerous) are cleared, then for a period of time allow for cell division to produce better "young" cells without DNA damaged and attached AGEs. This could be induced perhaps by consuming a high protein diet with leucine. 

 

3) Once you have produced more "good" cells, go through another cycle of fasting and supplementation to induce autophagy yet again. 

 

My guess is that if you can time each of this phases correctly (so that the percentage of healthy cells free of DNA damage goes up and the percentage of senescent/cancerous/damaged cells go down) the aging process would reverse. 

 

Timing everything could be tricky, though. Also, getting the supplementation right would be tough. 

 

However, I'm all for NR supplementation. The fact it boosts all the SIRT genes as well as reversing DNA damage via PARP seems let a net win (even though there may be some negatives)

[Rick Flair]

It was never my intention to post anything on this thread. I posted on another thread in response to MikeDC posting inaccurate information with the intent of disrupting a topic. Which he did. I could care less about anything MikeDC says on this thread. Very weak moderators. Apparently, a guy like MikeDC can go to any topic thread and post that his favorite vitamin is the best thing ever, and that is just ok.

[stefan_001]

It was never my intention to post anything on this thread. I posted on another thread in response to MikeDC posting inaccurate information with the intent of disrupting a topic. Which he did. I could care less about anything MikeDC says on this thread. Very weak moderators. Apparently, a guy like MikeDC can go to any topic thread and post that his favorite vitamin is the best thing ever, and that is just ok.

 

He has an optimistic tendency but given you joined this forum 3-4 days ago you got rather irritated fast and all your posts are about that......Perhaps comment/reject the statements with fact based arguments instead? That would certainly improve the discussion.

 

Rick Flair
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In Topic: Rapamycin vs NMR or NMN

Today, 05:51 PM

It was never my intention to post anything on this thread. I posted on another thread in response to MikeDC posting inaccurate information with the intent of disrupting a topic. Which he did. I could care less about anything MikeDC says on this thread. Very weak moderators. Apparently, a guy like MikeDC can go to any topic thread and post that his favorite vitamin is the best thing ever, and that is just ok.

 

In Topic: New Rapamycin Study- up to 60% increase in mouse lifespan- Anyone Experimenti...

Today, 02:59 PM

I have to call out the moderators on this site for being weak and ineffective. This was a great thread with people sharing experiences and ideas. But they let MikeDC hijack the thing.

 

In Topic: Glucosamine - is it entirely worthless?

Yesterday, 06:06 AM

MikeDC, paid troll selling vitamins.

 

In Topic: New Rapamycin Study- up to 60% increase in mouse lifespan- Anyone Experimenti...

Yesterday, 05:58 AM

Let's stick to the point. You lie while promoting this vitamin. Your a liar. Don't you get it. I predict that anything I say will be disregarded and you will continue to lie. Your an empty drum that keeps on beating. Shame on you.

 

In Topic: New Rapamycin Study- up to 60% increase in mouse lifespan- Anyone Experimenti...

Yesterday, 05:19 AM

    MikeDC, on 07 Aug 2017 - 05:06 AM, said:

    I know what you meant when you say vitamin. You think a vitamin will not help and useless while a big pharma drug with tons of side effects can.

Back to the lies. No such "tons of side effects" at 6mg per week. You are either slow, or your a low character.

 

 

Edited by stefan_001, 08 August 2017 - 03:28 PM.

[Valijon]

MikeDC is a big time proponent of NR and owns who knows how many shares of Chromadex so he is financially invested in the success of this product. Im personally ignoring anything else related to increasing NAD+ until many more concrete studies are published.

[Evan Yang]

MikeDC is a big time proponent of NR and owns who knows how many shares of Chromadex so he is financially invested in the success of this product. Im personally ignoring anything else related to increasing NAD+ until many more concrete studies are published.

 

Time will tell who is right. The science is there for the case of NAD+ deficit as the most important mechanism of aging and cancer. 

 

https://www.ncbi.nlm...pubmed/28780936

[Jaris]

For a fairly up-to-date comparison of NMN vs NR: http://alivebynature...st-nad-booster/

 

Can anyone explain the 2 apparently contradictory sentences, both take from the above page?

 

Fans of NMN such as Dr Sinclair claim that since NR must first be converted to NMN, it is more efficient to supplement with NMN as it is only 1 step away from NAD+.

 

Those like Dr Brenner who favor NR point out that that NMN cannot cross the cell membrane, but must first be converted to NR (r,r).

As depicted in the image, it is NMN > NR  (enter cell) > NMN > NAD+.  This would SEEM to favor NR, but we do not have  a good consensus on this question.

Also, this was interesting: The studies on Freidrichs Ataxia mentioned above seem to favor NMN, as it was able to restore cardiac function, whereas NR did not work in a similar experiment.

Edited by Jaris, 27 August 2017 - 11:18 PM.

[able]

For a fairly up-to-date comparison of NMN vs NR: http://alivebynature...st-nad-booster/

 

Can anyone explain the 2 apparently contradictory sentences, both take from the above page?

 

Fans of NMN such as Dr Sinclair claim that since NR must first be converted to NMN, it is more efficient to supplement with NMN as it is only 1 step away from NAD+.

 

Those like Dr Brenner who favor NR point out that that NMN cannot cross the cell membrane, but must first be converted to NR (r,r).

As depicted in the image, it is NMN > NR  (enter cell) > NMN > NAD+.  This would SEEM to favor NR, but we do not have  a good consensus on this question.

Also, this was interesting: The studies on Freidrichs Ataxia mentioned above seem to favor NMN, as it was able to restore cardiac function, whereas NR did not work in a similar experiment.

 

Interesting.  

 

My understanding is that, NMN is a very small step away from NAD+, and is not a rate limited process, so easily converted in bloodstream.  And, NMN is normally found in the bloodstream, so that favors NMN.  Also, it seemed to work better in the Fredric's Ataxia experiments.

 

On the other hand, Dr Brenners team is constantly finding new experiments to prove NR enters the cell membrane, but NMN must first be converted to NR to enter.  So, NMN can quickly convert to NAD+ in the liver, or, traverse the blood to a cell where it must convert to NR to enter a cell.  Which seems to favor NR.

 

I did stumble across a paper that showed NAD+ can cross the cell membrane itself, although that seems to be disputed quite often, so idk what the truth is on that.  

 

 

“Taken together, our findings, on the one hand, strengthen the hypothesis that eNAD crosses the plasma membrane intact and, on the other hand, provide evidence that increased NAD contents significantly affects mitochondrial bioenergetics and sensitivity to apoptosis.”

 

 

NMN or NR?  I don't know why it has to me one of the other.  If/when NMN comes down in price, I plan on taking both, along with my 1,000 mg a day of niacin.

 

Edited by able, 28 August 2017 - 01:19 AM.

[Evan Yang]

This is another study from Brenner that shows NMN needs to convert to NR before entering cell.

NAD+ is less effective than NR sincce it needs to break down to NMN and then NR to enter cell.

 

https://www.ncbi.nlm...ubmed/28842432/

Attached Files

•  Nicotinamide riboside, a form of vitamin B3, protects against excitotoxicity-induced axonal degeneration (3).pdf   1.98MB   0 downloads

Edited by Evan Yang, 28 August 2017 - 01:19 PM.

[Michael]

This is another study from Brenner that shows NMN needs to convert to NR before entering cell.

NAD+ is less effective than NR sincce it needs to break down to NMN and then NR to enter cell.

 

https://www.ncbi.nlm...ubmed/28842432/

 

But (as I indicated yesterday elsewhere), this has only been shown in vitro, which isn't a convincing way to show a meaningful advantage.  There's evidence that little or no NR is actually transported in the blood beyond the liver after oral administration: no one has yet detected it in the plasma beyond the hepatic loop (though that may just be because it's difficult to assay in the complex environment of serum/plasma), and a couple of studies have reported evidence that seems to suggest that it's actually converted to NAM after undergoing liver metabolism. So after orally administering NR, tissues outside of the liver in vivo may only ever actually be exposed to NAM, NA, or NMN (or NR derived from extracellular NMN — which has been detected in circulation in vivo after oral administration).

Edited by Michael, 29 August 2017 - 02:16 PM.

[stefan_001]

 

This is another study from Brenner that shows NMN needs to convert to NR before entering cell.

NAD+ is less effective than NR sincce it needs to break down to NMN and then NR to enter cell.

 

https://www.ncbi.nlm...ubmed/28842432/

 

But (as I indicated yesterday elsewhere), this has only been shown in vitro, which isn't a convincing way to show a meaningful advantage.  There's evidence that little or no NR is actually transported in the blood beyond the liver after oral administration: no one has yet detected it in the plasma beyond the hepatic loop (though that may just be because it's difficult to assay in the complex environment of serum/plasma), and a couple of studies have reported evidence that seems to suggest that it's actually converted to NAM after undergoing liver metabolism. So after orally administering NR, tissues outside of the liver in vivo may only ever actually be exposed to NAM, NA, or NMN (or NR derived from extracellular NMN — which has been detected in circulation in vivo after oral administration).

 

 

I am guessing the axonal degeneration study was done with a medical application in mind and not for showing oral NR effectiveness e.g. this could evolve into treatments using intracortical administration of NR.

 

My understanding was that the the orally taken NR boosts a range of metabolites simultaneously in the blood including NMN but that circulating NR is not detected. The interesting part is however that it is better at doing this than NAM, NMN etc. Also due to an increase in NAD+ reduction there is a NAM increase that in turn leads to second wave of NAD+ increase.
 

Edited by stefan_001, 29 August 2017 - 08:50 PM.