2255 replies to this topic

[Nate-2004]

 

 

Nobel Laureate Roger Kornberg is on the scientific advisory board so my guess is that ChromaDex's studies have been legit. 

 

But they haven't. Many of the studies Brian has posted look very promising but ChromaDex's "studies", at least the "published" one on a poster from April this year had a very small sample size and no controls.  That's not quality or legit IMO. 

 

That said, ChromaDex only has a license from Dartmouth to manufacture the NR, Dartmouth has the patent. They could easily take it away (if there is some legal language that this behavior is in violation of the license) and give it to someone else. I wouldn't worry about NR's reputation, it stands on its own I think.

 

 

A small sample size doesn't mean that the study is not legit. It means that it has a small sample size which is usually used to see if a larger study is worth it. 

 

 

Fair point, but no controls? 

[bluemoon]

 

 

 

Nobel Laureate Roger Kornberg is on the scientific advisory board so my guess is that ChromaDex's studies have been legit. 

 

But they haven't. Many of the studies Brian has posted look very promising but ChromaDex's "studies", at least the "published" one on a poster from April this year had a very small sample size and no controls.  That's not quality or legit IMO. 

 

That said, ChromaDex only has a license from Dartmouth to manufacture the NR, Dartmouth has the patent. They could easily take it away (if there is some legal language that this behavior is in violation of the license) and give it to someone else. I wouldn't worry about NR's reputation, it stands on its own I think.

 

 

A small sample size doesn't mean that the study is not legit. It means that it has a small sample size which is usually used to see if a larger study is worth it. 

 

 

Fair point, but no controls? 

 

 

I'm not sure of the study. What I meant is that I thought "legit" meant no fraud. It could still be junk science in which case it wouldn't be legit in a slightly different way. If I recall correctly, the larger one they are starting has controls for placebo effect. 

[Ethic]

Extracellular Nampt (eNampt) is a major contributor to inflammation, according to James Watson's latest article:

 

http://www.anti-agin...n-inflammation/

[Tom Andre F. (ex shinobi)]

thank you ethic. These guys are always one or 2 steps in advance

 

So it brings another question: is it possible to control also the iNampt / eNampt ? and if so is there a link with NAD+/NADH

 

It seems closely related: belly fat / energy expendure etc

 

I might have a closer loook into that

[stefan_001]

thank you ethic. These guys are always one or 2 steps in advance

 

So it brings another question: is it possible to control also the iNampt / eNampt ? and if so is there a link with NAD+/NADH

 

It seems closely related: belly fat / energy expendure etc

 

I might have a closer loook into that

 

Probably most know this but it is good it is also said in this article "NAMPT generates nicotinamide mononucleotide NMN from nicotinamide. NMN is then converted to NAD via nicotinamide riboside (NR)".

 

Gotta love the NR shortcut, it lets you nicely bypass the NAMPT controversy.

Edited by stefan_001, 22 June 2016 - 12:45 PM.

[Tom Andre F. (ex shinobi)]

 

thank you ethic. These guys are always one or 2 steps in advance

 

So it brings another question: is it possible to control also the iNampt / eNampt ? and if so is there a link with NAD+/NADH

 

It seems closely related: belly fat / energy expendure etc

 

I might have a closer loook into that

 

Probably most know this but it is good it is also said in this article "NAMPT generates nicotinamide mononucleotide NMN from nicotinamide. NMN is then converted to NAD via nicotinamide riboside (NR)".

 

Gotta love the NR shortcut, it lets you nicely bypass the NAMPT controversy.

 

 

its probably the case yes since the ribose help it to enter the cell, so then could be: NMN > NR > NMN (via NRK1.2) > NAD+ (via NMNAT1-3)

 

nicotinic acid also do not use NAMPT (Preiss-Handler pathway)

 

and you still get Nam at the end from 2 things:

 

1: NR being metabolized into Nam: "Recent work investigating the effects of nicotinamide riboside in yeast and mammals established that it is metabolized by at least two types of metabolic pathways. The first of these is degradative and produces nicotinamide. The second pathway involves kinases called nicotinamide riboside kinases (Nrk1 and Nrk2, in humans)." http://www.ncbi.nlm....pubmed/24071780

 

2: the NAD+ consuming enzyme...

 

But its nothing reltated to the article on their site.

 

[APBT]

FULL TEXT:

 

 

 

Attached Files

•  NR, a trace nutrient in foods......pdf   276.44KB   14 downloads

[Nate-2004]

Extracellular Nampt (eNampt) is a major contributor to inflammation, according to James Watson's latest article:

 

http://www.anti-agin...n-inflammation/

 

Wow that article is quite a load of information. From that article:

 

“Nicotinamide phosphoribosyltransferase (NAMPT), the key NAD+ biosynthetic enzyme, has two different forms, intra- and extracellular (iNAMPT and eNAMPT), in mammals. However, the significance of eNAMPT secretion remains unclear. Here we demonstrate that deacetylation of iNAMPT by the mammalian NAD+-dependent deacetylase SIRT1 predisposes the protein to secretion in adipocytes. NAMPT mutants reveal that SIRT1 deacetylates lysine 53 (K53) and enhances eNAMPT activity and secretion. —“

 

Does this mean that SIRT1 activated as a result of increased NAD+ will then cause eNAMPT secretion resulting in inflammation? In other words SIRT1 also is a good and bad thing...?

Edited by Nate-2004, 22 June 2016 - 02:01 PM.

[Tom Andre F. (ex shinobi)]

 

Extracellular Nampt (eNampt) is a major contributor to inflammation, according to James Watson's latest article:

 

http://www.anti-agin...n-inflammation/

 

Wow that article is quite a load of information. From that article:

 

“Nicotinamide phosphoribosyltransferase (NAMPT), the key NAD+ biosynthetic enzyme, has two different forms, intra- and extracellular (iNAMPT and eNAMPT), in mammals. However, the significance of eNAMPT secretion remains unclear. Here we demonstrate that deacetylation of iNAMPT by the mammalian NAD+-dependent deacetylase SIRT1 predisposes the protein to secretion in adipocytes. NAMPT mutants reveal that SIRT1 deacetylates lysine 53 (K53) and enhances eNAMPT activity and secretion. —“

 

Does this mean that SIRT1 activated as a result of increased NAD+ will then cause eNAMPT secretion resulting in inflammation? In other words SIRT1 also is a good and bad thing...?

 

 

I wouldnt feel concern about that. As they explain its a kind of response to CR for instance.

 

[Harkijn]

Yes, please let's keep some focus here. The very essence of this thread, you could say, is how to boost NAD+ while avoiding NAMPT. So far we have two approaches: NMN and NR.  Now the interview I linked to earlier today speaks of spectacular succes by involving TFAM. Perhaps it sinks in better if a paste a quote:

 

'Now your lab showed that there is a very exciting gene engineering alternative involving TFAM (Transcription Factor A, Mitochondrial). Why is TFAM important, and what have you done with it?

Church: TFAM is a key regulatory protein that is in this pathway of NMN and NAD+. It allows cells to manufacture the NMN precursor on their own, so you don't have to manufacture it outside the cell and then try to get it into the cell from outside. Ideally, you don't want to have to take NMN for the rest of your life, you want to fix the body's ability to make its own NMN and buy yourself rejuvenation for at least a few decades before you have to worry about NMN again. In order to accomplish this on a single cell level, we've used CRISPR to activate a TFAM activator, and we made it semi-permanent. 

Fahy: With this technique, you were able to increase TFAM levels in the cell by 47-fold. This resulted in restored ATP levels, increased NAD+, and an increased NAD+/NADH ratio. It also increased total mitochondrial mass and reversed several other age-related changes.

Church: Yes. We have a number of ways to measure mitochondrial function and age-related losses of those functions. When we activated TFAM, these changes returned to what you would expect of a younger cell state. And we built this anti-aging ability into the cell, so it's self-renewing and eliminates the need to take pills or injections. (Italics mine)

However, I looked up TFAM this afternoon and did find nothing as yet about involvement in NADproduction. The info I saw referred to a role more 'downstream'. Anyone aware of useful sources?

[stefan_001]

Yes, please let's keep some focus here. The very essence of this thread, you could say, is how to boost NAD+ while avoiding NAMPT. So far we have two approaches: NMN and NR.  Now the interview I linked to earlier today speaks of spectacular succes by involving TFAM. Perhaps it sinks in better if a paste a quote:

 

'Now your lab showed that there is a very exciting gene engineering alternative involving TFAM (Transcription Factor A, Mitochondrial). Why is TFAM important, and what have you done with it?

Church: TFAM is a key regulatory protein that is in this pathway of NMN and NAD+. It allows cells to manufacture the NMN precursor on their own, so you don't have to manufacture it outside the cell and then try to get it into the cell from outside. Ideally, you don't want to have to take NMN for the rest of your life, you want to fix the body's ability to make its own NMN and buy yourself rejuvenation for at least a few decades before you have to worry about NMN again. In order to accomplish this on a single cell level, we've used CRISPR to activate a TFAM activator, and we made it semi-permanent. 

Fahy: With this technique, you were able to increase TFAM levels in the cell by 47-fold. This resulted in restored ATP levels, increased NAD+, and an increased NAD+/NADH ratio. It also increased total mitochondrial mass and reversed several other age-related changes.

Church: Yes. We have a number of ways to measure mitochondrial function and age-related losses of those functions. When we activated TFAM, these changes returned to what you would expect of a younger cell state. And we built this anti-aging ability into the cell, so it's self-renewing and eliminates the need to take pills or injections. (Italics mine)

However, I looked up TFAM this afternoon and did find nothing as yet about involvement in NADproduction. The info I saw referred to a role more 'downstream'. Anyone aware of useful sources?

 

While this is certainly promising I think at best this is many years out in the future. Even if approved it would require all your current mitochondria to be replaced, not sure how realistic that is. Perhaps this could be a seperate thread?

[Bryan_S]

eNAMPT has both a “cytokine effect” and an “enzyme effect”

 

As we keep saying its all about blunting inflammation and "within the cell" I'm not convinced we need to stimulate NAMPT production because for some reason its leaking into our extracellular spaces and doing us harm.

 

I'm also not so quick to jump on the CRISPR bandwagon until we see it working in animal models and can map the ramifications. I look at that technology as a brute force method because we lack the underlying epigenetic understanding of why these pathways change with age. Why permanently change something that is supposed to work in tandem with other pathways through feedback loops. I think the NAD+ repletion method is the best path until these other techniques mature enough to know their ramifications and potential uses.

 

Guys/Gals we are standing on the bleeding edge. We don't know what discovery will be uncovered next and offer insight into the next step forward.

 

I think what's happened in the last few years is NAD+ has become recognized as one of the major players in aging. Surrounding this is the salvage pathway that helps recapture the NAM from those ATP and NAD reactions and many thought this might be failing with age. However today we realize there are possibly other imbalances like this CD38 that begins to weigh down on our NAD production and consume it. If this enzyme is destroying our NAD at ever increasing levels as we age, don't we want to understand what up-regulated this before we go editing our genome to produce more NAD? I still want to see more research dedicated to CD38 period!

 

We are going to see this landscape change. We are all aging and we want answers while we are still around to benefit from them. NAD+ boosting or NAD+ repletion as its being called will be eventually replaced with something else as our understanding changes. So as always I advocate taking a path that will do the most good and produce the least harm. For now that path appears to be NAD+ repletion. 

 

https://www.scienced...60428152124.htm

[Nate-2004]

Even if approved it would require all your current mitochondria to be replaced, not sure how realistic that is. 

 

Why?

[Nate-2004]

eNAMPT has both a “cytokine effect” and an “enzyme effect”

 

As we keep saying its all about blunting inflammation and "within the cell" I'm not convinced we need to stimulate NAMPT production because for some reason its leaking into our extracellular spaces and doing us harm.

 

I'm also not so quick to jump on the CRISPR bandwagon until we see it working in animal models and can map the ramifications. I look at that technology as a brute force method because we lack the underlying epigenetic understanding of why these pathways change with age. Why permanently change something that is supposed to work in tandem with other pathways through feedback loops. I think the NAD+ repletion method is the best path until these other techniques mature enough to know their ramifications and potential uses.

 

Guys/Gals we are standing on the bleeding edge. We don't know what discovery will be uncovered next and offer insight into the next step forward.

 

I think what's happened in the last few years is NAD+ has become recognized as one of the major players in aging. Surrounding this is the salvage pathway that helps recapture the NAM from those ATP and NAD reactions and many thought this might be failing with age. However today we realize there are possibly other imbalances like this CD38 that begins to weigh down on our NAD production and consume it. If this enzyme is destroying our NAD at ever increasing levels as we age, don't we want to understand what up-regulated this before we go editing our genome to produce more NAD? I still want to see more research dedicated to CD38 period!

 

We are going to see this landscape change. We are all aging and we want answers while we are still around to benefit from them. NAD+ boosting or NAD+ repletion as its being called will be eventually replaced with something else as our understanding changes. So as always I advocate taking a path that will do the most good and produce the least harm. For now that path appears to be NAD+ repletion. 

 

https://www.scienced...60428152124.htm

 

I agree, especially with the part about getting to the root of why CD38 is on the rise. I also don't see any harm in taking either apigenin or drinking plenty of chamomile tea in order to reduce the amount of CD38 if that's its mechanism of action.

[stefan_001]

 

Even if approved it would require all your current mitochondria to be replaced, not sure how realistic that is. 

 

Why?

 

 

To my understanding crispr cannot currently work across an adult system but can be used to modify the few cells in an early embryo, conferring the edit to all cells in the later adult as it grows. I guess you can inject cas9 inside the blood and from there find a way to get it into the cells but like said sounds to me that will be years away.

Edited by stefan_001, 22 June 2016 - 05:50 PM.

[stefan_001]

 

eNAMPT has both a “cytokine effect” and an “enzyme effect”

 

As we keep saying its all about blunting inflammation and "within the cell" I'm not convinced we need to stimulate NAMPT production because for some reason its leaking into our extracellular spaces and doing us harm.

 

I'm also not so quick to jump on the CRISPR bandwagon until we see it working in animal models and can map the ramifications. I look at that technology as a brute force method because we lack the underlying epigenetic understanding of why these pathways change with age. Why permanently change something that is supposed to work in tandem with other pathways through feedback loops. I think the NAD+ repletion method is the best path until these other techniques mature enough to know their ramifications and potential uses.

 

Guys/Gals we are standing on the bleeding edge. We don't know what discovery will be uncovered next and offer insight into the next step forward.

 

I think what's happened in the last few years is NAD+ has become recognized as one of the major players in aging. Surrounding this is the salvage pathway that helps recapture the NAM from those ATP and NAD reactions and many thought this might be failing with age. However today we realize there are possibly other imbalances like this CD38 that begins to weigh down on our NAD production and consume it. If this enzyme is destroying our NAD at ever increasing levels as we age, don't we want to understand what up-regulated this before we go editing our genome to produce more NAD? I still want to see more research dedicated to CD38 period!

 

We are going to see this landscape change. We are all aging and we want answers while we are still around to benefit from them. NAD+ boosting or NAD+ repletion as its being called will be eventually replaced with something else as our understanding changes. So as always I advocate taking a path that will do the most good and produce the least harm. For now that path appears to be NAD+ repletion. 

 

https://www.scienced...60428152124.htm

 

I agree, especially with the part about getting to the root of why CD38 is on the rise. I also don't see any harm in taking either apigenin or drinking plenty of chamomile tea in order to reduce the amount of CD38 if that's its mechanism of action.

 

 

So how would you setup your experiment? What markers are you planning to check to see whether this is usefull against your baseline NR? 

[Nate-2004]

So how would you setup your experiment? What markers are you planning to check to see whether this is usefull against your baseline NR? 

 

 

Are you suggesting I wash out for a week, get blood work done, then take NR, get blood work done, then take apigenin with the NR and get blood work done again to gets pre NR, post NR and post Apigenin levels of NAD? Has anyone here done this for NR?

 

Since starting Apigenin with NR two days ago I do feel I have even more energy than I had with just the NR. I'm not sure if that's placebo or what. That aside, apigenin is also said to be an aromatase inhibitor which sounds good to me as I'd definitely like to boost my testosterone levels.

Edited by Nate-2004, 22 June 2016 - 06:48 PM.

[Harkijn]

 

Yes, please let's keep some focus here. The very essence of this thread, you could say, is how to boost NAD+ while avoiding NAMPT. So far we have two approaches: NMN and NR.  Now the interview I linked to earlier today speaks of spectacular succes by involving TFAM. Perhaps it sinks in better if a paste a quote:

 

'Now your lab showed that there is a very exciting gene engineering alternative involving TFAM (Transcription Factor A, Mitochondrial). Why is TFAM important, and what have you done with it?

Church: TFAM is a key regulatory protein that is in this pathway of NMN and NAD+. It allows cells to manufacture the NMN precursor on their own, so you don't have to manufacture it outside the cell and then try to get it into the cell from outside. Ideally, you don't want to have to take NMN for the rest of your life, you want to fix the body's ability to make its own NMN and buy yourself rejuvenation for at least a few decades before you have to worry about NMN again. In order to accomplish this on a single cell level, we've used CRISPR to activate a TFAM activator, and we made it semi-permanent. 

Fahy: With this technique, you were able to increase TFAM levels in the cell by 47-fold. This resulted in restored ATP levels, increased NAD+, and an increased NAD+/NADH ratio. It also increased total mitochondrial mass and reversed several other age-related changes.

Church: Yes. We have a number of ways to measure mitochondrial function and age-related losses of those functions. When we activated TFAM, these changes returned to what you would expect of a younger cell state. And we built this anti-aging ability into the cell, so it's self-renewing and eliminates the need to take pills or injections. (Italics mine)

However, I looked up TFAM this afternoon and did find nothing as yet about involvement in NADproduction. The info I saw referred to a role more 'downstream'. Anyone aware of useful sources?

 

While this is certainly promising I think at best this is many years out in the future. Even if approved it would require all your current mitochondria to be replaced, not sure how realistic that is. Perhaps this could be a seperate thread?

 

Don't hold your breath, but clinical trials expected within one year. Wish we could say that for NR! They do not want to replace mitochondria piece by piece, it works differently...

[Harkijn]

eNAMPT has both a “cytokine effect” and an “enzyme effect”

 

As we keep saying its all about blunting inflammation and "within the cell" I'm not convinced we need to stimulate NAMPT production because for some reason its leaking into our extracellular spaces and doing us harm.

 

I'm also not so quick to jump on the CRISPR bandwagon until we see it working in animal models and can map the ramifications. I look at that technology as a brute force method because we lack the underlying epigenetic understanding of why these pathways change with age. Why permanently change something that is supposed to work in tandem with other pathways through feedback loops. I think the NAD+ repletion method is the best path until these other techniques mature enough to know their ramifications and potential uses.

 

Guys/Gals we are standing on the bleeding edge. We don't know what discovery will be uncovered next and offer insight into the next step forward.

 

I think what's happened in the last few years is NAD+ has become recognized as one of the major players in aging. Surrounding this is the salvage pathway that helps recapture the NAM from those ATP and NAD reactions and many thought this might be failing with age. However today we realize there are possibly other imbalances like this CD38 that begins to weigh down on our NAD production and consume it. If this enzyme is destroying our NAD at ever increasing levels as we age, don't we want to understand what up-regulated this before we go editing our genome to produce more NAD? I still want to see more research dedicated to CD38 period!

 

We are going to see this landscape change. We are all aging and we want answers while we are still around to benefit from them. NAD+ boosting or NAD+ repletion as its being called will be eventually replaced with something else as our understanding changes. So as always I advocate taking a path that will do the most good and produce the least harm. For now that path appears to be NAD+ repletion. 

 

https://www.scienced...60428152124.htm

I agree with you Brian and I will certainly keep taking NR until more clarity arises but that does not exclude that this new  very practical approach will lead us to a lot of new insights, for instance perhaps about CD38 about which I am as uneasy as you. We are all excited about NR but when you look at the results achieved so far there are so many caveats ( like: it's in mice, it's in GM mice, it's in high fat diets etc.) and uncertainties about dosing that any input on NADboosting from a new angle is urgently required.

[Bryan_S]

Yes there has been a number of Animal studies. This is where it all begins but the human trials are progressing as well. Our questions have outpaced the research or the research released so far but information is coming and those writing the papers are not influenced by our hunger for results. Information on CD38 from other researchers will take time to confirm and since its a new angle in the NAD+ effort it will take time for the new investigative work to begin.

 

Welcome to the bleeding edge.

[Female Scientist]

Meanwhile, is the group feeling OK about the Chromadex stock price today, or do we need to start thinking about hoarding NR in case of some bad outcome that slows/stops production?

[Harkijn]

Yes there has been a number of Animal studies. This is where it all begins but the human trials are progressing as well. Our questions have outpaced the research or the research released so far but information is coming and those writing the papers are not influenced by our hunger for results. Information on CD38 from other researchers will take time to confirm and since its a new angle in the NAD+ effort it will take time for the new investigative work to begin.

 

Welcome to the bleeding edge.

Thx  Bryan, this gives some hope.

[stefan_001]

Meanwhile, is the group feeling OK about the Chromadex stock price today, or do we need to start thinking about hoarding NR in case of some bad outcome that slows/stops production?

 

Personally I am not too worried about Chromadex. The company is around for some 10 years and despite what the article says healthier financially when compared to previous years.

[stefan_001]

now what to think of this study:

 

http://www.sciencedi...047637416300926

 

NAM supplementation promotes extreme lifespan extension.

NAM supplementation promotes extreme lifespan extension.

[HappyPaul]

Meanwhile, is the group feeling OK about the Chromadex stock price today, or do we need to start thinking about hoarding NR in case of some bad outcome that slows/stops production?

I know this whole stock thing is OT for the intent of this post and I wish it all never came up, especially as I lost $.  I have been and remain a huge NR supporter but I have to separate the company from the NR.  Your question about NR availability is certainly a valid concern I did think of too. 

 

I feel a bit better with the release they made late today. http://www.nutraingr...paign=copyright

 

I would have been happier if it gave a name for customer C or used words to describe customer C like arms length, long time external customer, or company not owned or controlled by major stock holder etc.. were included but this does mute the specific attack that alluded to that it was Fried's company.  I still have some concerns specifically having to do with the history of some present and past board members and how and what other companies they were involved with did financially and with their stock but I would say the announcement and that the stock did not wildly fluctuate today is not bad and makes me far less concerned about NR supply.  

 

I can understand an awkward response and time if you get hit with something like this out of the blue but I would like to think that they had a plan prepared for when word came out about a board member being charged by the SEC.  I am willing to understand that they were not prepared and hope that this won't happen again but I also expect them to review their board and adjust if appropriate. 

 

I am not expecting NR supplies to be hit at this point but I caution this is all an uneducated and uniformed guesswork by me as I am just trying to figure it all out as are you.  Its up to the company to realize they have a bulls-eye on them and they need to be exceptionally transparent and make sure that no one ever has cause to question their ethics or motivations of the board members or major partners.  Hopefully this is a learning experience bump in the road and not a matter of the first of more things to come. 

[bluemoon]

I take a different view. I think it is unlikely Chromadex will be around in 2017. There is just way too much going against them and weak excuses to try to explain away bad elements. Yet they still control NR for now so it isn't clear what will happen to the stock price.   I have a friend who now thinks NR is b.s. because of this. "Where are the sharp investors if NR is so great?  

 

But as I try to explain ,it is about scientific results and not a company. And there are pharmaceuticals who will be formidable against supplement companies, and I think put most out of business.  

Edited by bluemoon, 23 June 2016 - 04:19 AM.

[Nate-2004]

Personally I hope this whole Chromadex results in cheaper prices rather than more expensive due to supply. I'm mainly worried about the cost. I may just take advantage of that 6 bottle deal from HPN right now instead of waiting till I'm out.

 

Back to NAD boosting, for those wanting to tackle CD38, I just discovered that apigenin has a half-life of 91 hrs in some reports and in others, at least 12 hrs. There are as many sources in a google search claiming the latter as there are claiming the former. It's not toxic but can make you sleepy. That's a wide range though, so not sure how I'll be dosing yet but I'll play with it for a week or two.

 

 

 

http://www.sciencedi...047637416300926

 

NAM supplementation promotes extreme lifespan extension.

NAM supplementation promotes extreme lifespan extension.

 

Extreme life expansion is a bold claim for an experiment on yeast. More promising results though. 

[stefan_001]

 

 

Yes, please let's keep some focus here. The very essence of this thread, you could say, is how to boost NAD+ while avoiding NAMPT. So far we have two approaches: NMN and NR.  Now the interview I linked to earlier today speaks of spectacular succes by involving TFAM. Perhaps it sinks in better if a paste a quote:

 

'Now your lab showed that there is a very exciting gene engineering alternative involving TFAM (Transcription Factor A, Mitochondrial). Why is TFAM important, and what have you done with it?

Church: TFAM is a key regulatory protein that is in this pathway of NMN and NAD+. It allows cells to manufacture the NMN precursor on their own, so you don't have to manufacture it outside the cell and then try to get it into the cell from outside. Ideally, you don't want to have to take NMN for the rest of your life, you want to fix the body's ability to make its own NMN and buy yourself rejuvenation for at least a few decades before you have to worry about NMN again. In order to accomplish this on a single cell level, we've used CRISPR to activate a TFAM activator, and we made it semi-permanent. 

Fahy: With this technique, you were able to increase TFAM levels in the cell by 47-fold. This resulted in restored ATP levels, increased NAD+, and an increased NAD+/NADH ratio. It also increased total mitochondrial mass and reversed several other age-related changes.

Church: Yes. We have a number of ways to measure mitochondrial function and age-related losses of those functions. When we activated TFAM, these changes returned to what you would expect of a younger cell state. And we built this anti-aging ability into the cell, so it's self-renewing and eliminates the need to take pills or injections. (Italics mine)

However, I looked up TFAM this afternoon and did find nothing as yet about involvement in NADproduction. The info I saw referred to a role more 'downstream'. Anyone aware of useful sources?

 

While this is certainly promising I think at best this is many years out in the future. Even if approved it would require all your current mitochondria to be replaced, not sure how realistic that is. Perhaps this could be a seperate thread?

 

Don't hold your breath, but clinical trials expected within one year. Wish we could say that for NR! They do not want to replace mitochondria piece by piece, it works differently...

 

 

I am not holding my breath, if you read the entire interview then its clear that there is quite a bit of speculation in the claims...also I assume you noticed this piece "On January 7, 2016, Dr. Church's company, Editas Medicine, filed papers to launch a $100 million IPO,". Nevertheless the study around aging factors is interesting but it didnt get clear to me who is actually doing those. Also using my entirely non-scientific evaluation on his appearance in pictures in the internet I concluded that he looks at least his age so whatever he talks about he is either not using himself already or then it doesnt work.

 

I will dig a bit too into TFAM nevertheless....

 

 

Edited by stefan_001, 23 June 2016 - 05:43 AM.

[Bryan_S]

Meanwhile, is the group feeling OK about the Chromadex stock price today, or do we need to start thinking about hoarding NR in case of some bad outcome that slows/stops production?

 

I can make no long term predictions. But I will say NAD+ Boosting or Repletion as they are calling it is not the end answer. We are all huddled here because at the moment this is the safest and simplest method of raising NAD+. I trust at some point we will totally understand what is killing our NAD pools and correct the problem. However this day is not today and its my hope (NR) production will survive until we wish to voluntarily drop it. If this supply comes under pressure before we wish to move on, there are still other NAD precursors to consider such as the NAM supplementation which was pointed out. So in the end, if the end were near, which is unlikely, we still have options that are better than doing simply nothing.

 

I myself took 2 grams pre day of NAM for more than a year. Its cheap and raises NAD levels. It might not ring all the right Sirtuin bells and whistles and it requires more NAMPT which we know has problems but it shouldn't be totally discounted. Then on the other hand you have Niacin. If you can take the flushing it has many of the same benefits as NR but can't be taken in as high a daily dose. Meaning check your blood-work and keep an eye on your liver. Still again if MNM becomes available at affordable rates (this link is not an incitement to buy) we may still have that option. So options abound even if economical ones dry up.

 

In answer to an earlier question I stocked up on NR but now feel that might have been a knee jerk reaction. I checked and HPN has extended their bimonthly discount at least a little while to provide for impulse buyers like me. So as a hoarder I'm good for the next few months in any event. 

Edited by Bryan_S, 23 June 2016 - 08:02 AM.

[stefan_001]

 

So how would you setup your experiment? What markers are you planning to check to see whether this is usefull against your baseline NR? 

 

 

Are you suggesting I wash out for a week, get blood work done, then take NR, get blood work done, then take apigenin with the NR and get blood work done again to gets pre NR, post NR and post Apigenin levels of NAD? Has anyone here done this for NR?

 

Since starting Apigenin with NR two days ago I do feel I have even more energy than I had with just the NR. I'm not sure if that's placebo or what. That aside, apigenin is also said to be an aromatase inhibitor which sounds good to me as I'd definitely like to boost my testosterone levels.

 

 

The entire topic of whether something is beneficial is in my view really difficult. Personally I have concluded that I can probably do regime changes every 2-3 months if I want to conclude anything. Short term effects like more or less energy I am not taking too serious anymore. So I watch:

- memory recall. How welll can I remember numbers for a short time. For work I regularly dial into conference calls with 9 digit ID codes, so do I remember better or not...either I dial wrong or right after looking at the number couple times.

- physical appearence. I have a pretty standard gym routine so is my body changing more or less

- hair. My hairline is on a slow recovery. Does it stay on track or stall

- eyesight. This has improved but still intermittent. I suspect lens stiffening cannot be easily overcome...

- skin, the ultimate challenge in my view. ECM in the face, wrinkless, elasticity

 

But all of those will only show changes in longer term. Just as example skin epidermal cells renew every 15-30 days. So if you want to see impact for example from epigenetic changes my guess is you would need couple months before something becomes visible. I have noticed people make fast changes to regimes but the body renewal doesn't go that fast in my opinion.

 

Personally I am very satisfied with NR, but I have added some polyphenols on the hypothesis to tamp inflammation for example. I have added those over time. It is not easy to say what each item does but I am fairly sure that the combination work. Of course each person in different and I am also convinced that other factors like the amount you eat and the exercise you do are other critical components. Exercise activates 100s of genes for example. Anyways I am 46 years old and last week I got offered a student card for a nightclub :-) that would not have happened 1-2 years ago so yeah I am not in a hurry to tweak my CD38s....I go for long and slow improvement just like aging which is long and slow but then resversed.

Edited by stefan_001, 23 June 2016 - 10:40 AM.