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Nicotinamide Riboside [Curated]

nicotinamide riboside nicotinamide nad boosting charles brenner david sinclair leonard guarente niagen niacinamide nicotinamide mononucleotide

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#1591 sthira

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Posted 26 November 2016 - 09:11 PM

Sheesh. Ya know, we've seen many great minds and writers and thinkers chased away in frustration from this (formerly more awesome) longevity site due to easy ad hom attacks like that one expressed above by blue moon.

Hey: wide angle lens: we're all in this frozen anti-aging drama together: nothing now slows, stops, or reverses aging yet: nothing: no matter how hard we dream and how much we'd like for some simple solution like a pill or a lifestyle behavior to do it: it ain't there. We're innocent babes. And vulnerable, we need all the objective, focused thinkers who aren't pushing some product on us for their own personal stock market gains, or whatever.

Michael Rae has contributed a huge amount of unbiased thought regarding the unpopular "science" of lifespan extension. I do have a biology degree and background, and I'm unable to follow along anywhere near as well as he does. Who has time to calmly investigate the many overly-optimistic claims brought to market by these for-profit-only supplement companies? One after another these companies -- they know they have us in a corner, they know they have a captive audience willing to spend, they know people are desperate and suffering -- and so they're eagerly making money off of our ignorance and despair.

And before I sway this back onto topic, consider this: Donald Trump has expressed sharp disdain for the US FDA, for the consumer regulatory process in general (since it protects consumers from predatory, dishonest corporations), and if he and the right wing are successful in relaxing consumer protection laws, we're gonna need help. We're gonna need to rely more often on unbiased thinkers like Rae to point out the relevant peer reviewed science that many of us are too busy to chase, to break down, and to figure out the difference between what's fake news and what's real. Fraud and hucksterism pervades the supplement industry, and with retarded regulation ahead, more fraud and hucksterism is likely headed our way.

The Longecity community should be encouraging thinkers -- Michael Rae is a SENS insider with valuable info to pass along -- don't push him out of these fora. Who gives a crap about Michael Rae's "science background" when he writes so coherently and well (backed with thorough references for nearly every post)?

Swerving the topic back onto ChromaDex's Niagen, I've still not seen answered -- despite the many studies posted here in this thread -- some basic questions presented by Rae here: http://www.sens.org/...ng-mitochondria

If you don't feel like reading that simple text, here are the issues:

(1) "...[I]t must be clarified that the substance used in the Harvard research was not actually NR, but another compound called nicotinamide mononucleotide (NMN). But NMN is unsuitable for oral supplementation, as it is rapidly hydrolyzed in the intestine, so the Harvard researchers (like a previous team of scientists from the Washington University School of Medicine at St. Louis and others thereafter) injected their mice with NMN rather than giving it to them in their feed...."

(2) "...[M]any supplement vendors assert or imply that the results with NMN can also be gained with NR. Promoters of NR also point to studies showing that NR yields improvements in metabolic health in rodent models of diabetic obesity promoted by a high-fat/high sugar diet that are similar to those reported for injected NMN. These vendors furthermore note positive results of NR supplementation in mouse models of genetic neurological and mitochondrial disorders, and in mice genetically engineered to develop liver cancer..."

(3) "...[N]o study has actually been done demonstrating that NR has similar effects to NMN in the muscles of otherwise-healthy aging mice. In fact, one study found that high-dose NR supplementation was unable to increase NAD+­ levels in muscle tissue or the mitochondrial fraction of normal, healthy mice...."

(4) "...Moreover, even if NR supplements do provide an immediate jolt to muscle mitochondrial metabolism in the way that the Harvard NMN studies suggest, it’s not clear that doing so is a good idea in the long term. NMN injections don’t improve mitochondrial function by repairing molecular damage wrought by the aging process in the organelles, nor in other cells and biomolecules whose damage with age results in a dampening-down of mitochondrial activity..."

(5) "...Instead, NMN injections leave the existing damage in place, and induce the still-functional mitochondria to work harder and pump out more energy. This is rather like pushing harder on the gas pedal when your car is not running at full power due to damage to its cams and push rods: it may make the car go faster in the short term, but the underlying damage hasn’t been fixed, and will likely get even worse from the excessive wear..."

(6) "...Because the Harvard study of NMN-treated mice only lasted a week, it did not examine the long-term effects of NMN treatment on the mice. Previous studies with other dietary supplements, however, have revealed that the potential for such effects does exist and cannot be neglected in risk/benefit evaluations...."

(7) "...It’s also important for readers of the press coverage of the Harvard report to understand just what was involved when such stories reported that NMN treatment “reversed the effects of aging” on the mice’s muscles. Readers would be forgiven for imagining the muscles of frail, elderly mice suddenly swelling to youthful size, able to perform tiny rodent bench presses with the strength and endurance of much younger animals. In reality, though, as the investigators were careful to point out in the original scientific paper, while their treated animals’ muscle cells exhibited biochemical evidence of improved (“rejuvenated”) metabolism and insulin-stimulated glucose uptake, “we did not observe an improvement in muscle strength (data not shown), indicating that 1 week of treatment might not be sufficient to reverse whole-organism aging and that longer treatments might be required.”

(8) "...Additionally, interpretation of the Harvard report is greatly hampered by the lack of information of the animals’ weight or food intake, which raises the possibility of effects mediated by Calorie restriction or (contrariwise) by the simple overfeeding of all the animals in the study.

(9) "Also, an earlier report by Dr. Shin-ichiro Imai of the Washington University School of Medicine at St. Louis, who was a pioneer in working with this compound, had identified some gender-discordant effects of NMN on glucose metabolism, and unfortunately the Harvard report does not disclose the sex of the animals. In fact, some of the reported findings in the new report seem to be contradicted by Dr. Imai’s earlier studies. It will be good to see these issues clarified and ironed out in future research."

(10) "....The studies showing benefits of NR supplementation in mouse models of disease have used doses of 400-500 milligrams of NR per kilogram of mouse body weight. Even after adjusting for the different metabolic rates of mice and humans, an approximate equivalent adult dose would range from 2000 to 4000 milligrams of NR per day. Commercially-available NR supplements contain between 75 and 125 mg NR per capsule, at a cost of roughly 0.6-0.8 cents per milligram of NR; to experiment with even the lower end of the human-equivalent dosage range would thus involve swallowing 18-30 NR pills a day, at a cost of $400-550 a month."

Has any progress been made here? Maybe some progress has been made here, and I've just missed it? This is a very long thread indeed.

Focus this thread on answering some of dat shit, man, instead of pulling up some speech from 2008 (which, btw, I still can't wrap my head around the fact that Michael Rae is "six feet tall and weighs 115 pounds..." Is that shit still true?! Damned! people tell me I'm way to skinny and I'm 6'2" 145....

Appeal: don't blow this light-heavy weight away with more rudeness because when you do, the entire community here loses. And we've seen that ugliness happen to many great contributors in the past, sadly & repeatedly
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#1592 bluemoon

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Posted 26 November 2016 - 09:36 PM

Sheesh. Ya know, we've seen many great minds and writers and thinkers chased away in frustration from this (formerly more awesome) longevity site due to easy ad hom attacks like that one expressed above by blue moon.   

 

Please look up the meaning of "ad hominem."  There was no ad hominem attack anywhere in my posts. I pointed out some of the basics that Michael Rae got wrong, like no increase in longevity since 1950 apart from reduction in childhood deaths. Nobody has been "chased away."


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#1593 midas

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Posted 26 November 2016 - 09:37 PM

(1) "...[I]t must be clarified that the substance used in the Harvard research was not actually NR, but another compound called nicotinamide mononucleotide (NMN). But NMN is unsuitable for oral supplementation, as it is rapidly hydrolyzed in the intestine, so the Harvard researchers (like a previous team of scientists from the Washington University School of Medicine at St. Louis and others thereafter) injected their mice with NMN rather than giving it to them in their feed...."

 

The new study shows that when NMN is dissolved in drinking water and given to mice, it appears in the bloodstream in less than three minutes. Importantly, the researchers also found that NMN in the blood is quickly converted to NAD in multiple tissues.

 

https://medicine.wus...g-healthy-mice/

 

 

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(3) "...[N]o study has actually been done demonstrating that NR has similar effects to NMN in the muscles of otherwise-healthy aging mice. In fact, one study found that high-dose NR supplementation was unable to increase NAD+­ levels in muscle tissue or the mitochondrial fraction of normal, healthy mice...."

 

https://infoscience....h/record/223053

 


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#1594 sthira

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Posted 26 November 2016 - 11:05 PM

Ok, yep, it's a rainy cold grey (not de Gray) Saturday here in a cozy coffee shop in a gentrified neighborhood so I guess we'll have to stay off topic for a bit -- do chuck thesesesese ssilly posts out the backdoor when ya can -- but meanwhile, yes thank you, bluemoon maybe I indeed don't know the def of "ad hominem" blah bleh this'll go fucking nowhere but hey cheer up: https://en.m.wikiped...wiki/Ad_hominem

"Ad hominem (Latin for "to the man" or "to the person"[1]), short for argumentum ad hominem, is a logical fallacy in which an argument is rebutted by attacking the character, motive, or other attribute of the person making the argument, or persons associated with the argument, rather than attacking the substance of the argument itself."

Is this an example of ad hominem?

I watched Michael in a 2008 TED talk and thought he was 1) a zealot about CR and 2) sloppy at times."


So if I called you a sloppy zealot to you in person you wouldn't punch me in the face?

Ok so then do these two little swipes rise over the high bar def?

Michael has no science background whatsoever, and that should be kept in mind. Rae is a cheerleader, and we need those.


I say 1+1=3 and you say naw man that shit ain't right because you have no maths background whatsoever. And, furthermore, you're a cheerleader (which I admit is an compliment, actually, since cheerleaders are amazing athletes). But you've said he's a (verbal) cheerleader for his guru, so I don't know, man, that sounds not very friendly to me.

Ok, I'm still not reaching you; but this'll be over soon, I promise; then we'll hug and purchase more Niagen and finally -- oh thank god finally -- we'll stop all metabolic and gravitational aging damage with NR

But imagine you're there enjoying your coffee and I walk up, sit down, hi, hey, we talk, we eventually disagree about NR, and then you say:

....[You] throw around "exponentially downward curve" without any idea what an exponential is. What is [your] science background? Nothing.


This isn't mean? Even after too much caffeine you prob wouldn't say this to anyone in person, would you?

By the way, my undergrad degrees are in physics and mathematics - no biologist here! :) What is your science background, Michael since you implied above that you have a science background of some sort, so can you tell us what it is? I think nothing since high school. Again, I applaud your cheerleading because that does help.


Now your turn! Please tell me next how I'm still not understanding common words and phrases!

Also, I do think talking unkindly to and about people "chases them away..." and in this case you've met those standards at least according to me.

Believe it or not, I, too, would like to keep reading about NR. I'm just tired of being hoodwinked by these companies making false promises ahead of the science to we the people.

And I'd like to see more writing from Michael Rae here, not less. Hence my slathering sloppy cheerleaderism haha
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#1595 prophets

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Posted 26 November 2016 - 11:22 PM

 

 

Please look up the meaning of "ad hominem."  There was no ad hominem attack anywhere in my posts. I pointed out some of the basics that Michael Rae got wrong, like no increase in longevity since 1950 apart from reduction in childhood deaths. Nobody has been "chased away."

 

 

You constantly derail this thread into ancillary discussion that have nothing to do with Nicotinamide Riboside.  You are constantly going down rabbit holes, attacking people, chasing some side story that is away from the main discussion issue of NR.

 

You fuck up this thread more than anyone here.  It's beyond irritating.  Maybe somewhere between your studies of topology and real analysis, on your way to a math degree, you could have picked up some coursework in common sense.

 

Even if Michael Rae had zero academic training in biology, chemistry and the life sciences, just the fact that he's worked 10+ years in the life extension area -- in and around leading scientists in the field with a serious funding effort, has granted him a high level of exposure and experience that most do not have.  There aren't a lot of people like Michael Rae who have been working on these issues related to lifespan for such a lengthy period of time.  His opinion/views may be wrong.  They may not be the only opinion.  But they are certainly not valueless.


Edited by prophets, 26 November 2016 - 11:27 PM.

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#1596 bluemoon

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Posted 26 November 2016 - 11:39 PM

Rewind the thread. I have not derailed at any point. The two recent examples: a guy posts about what he considers to be a high risk of NR causing cancer. I show where at least NMN doesnt seem to, etc and some how I am the one going off topic? The same when Kevin criticized Michael Rae and more than I did. I was responding to what was already on the page.

 

If Michael Rae has worked so long with longevity, then why didn't he know the basic fact that longevity in the West since 1950 has increased about 6 or 7 years unrelated to child mortality? And yeah, I guess it annoys me when the hyperbolic throw around "exponential change" when nothing of the sort happened.

 

Anyway prophets, I'm sorry I worked you up into a little hissy fit. 

 

 

 


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#1597 Michael

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Posted 26 November 2016 - 11:42 PM

Sigh ...
 

Here is a short 7 minute version of his 15 minute talk in 2008. Please tell me where I have been wrong or misleading.


Throughout ;) .
 

You know, I didn't nitpick his 2008 presentation when he throws around "exponentially downward curve" without any idea what an exponential is. What is his science background? Nothing.

 

I described the "downward exponential curve of biological aging" (≈2:20), referring to the (yes) exponential increase of morbidity and mortality rate with age. I'll acknowledge a tiny bit of slop elsewhere in describing the survival curve itself as simply following an exponential, since it is the interaction of the age-dependent and age-independent components, but suggesting that this demonstrates a complete lack of scientific background is completely unreasonable.
 

He says in this presentation that "It hasn't been since 1950 since we've made much change" in longevity which is way off as around 6 years have been added in the past 60 years apart from an increase due to lower childhood mortality.


(a) One year per decade in median lifespan is better than nothing, but hardly the kind of heroic progress made against child and infant mortality in from the late 1800s to mid-twentieth century, and for lack of progress against aging and late-life mortality, which was the subject at hand.

 

(b) The full quote is, "it hasn't been, since 1950, that we've made much change at the far end" (emphasis added). Median LS of course still incorporates ongoing progress in lowering deaths childhood mortality, and "premature" mortality in midlife.

 

[c) Even some of the progress in lowering relatively late-life mortality represents the long-term outcomes of better antenatal and child nutrition and infection control (the Barker hypothesis and related work by Finch and Crimmins).
 

I don't think Rae remembers his statement about De Gray at 4:10 in the link below. "He doesn't say 10 years, he says 25! (laughs)" Again, no he doesnt. He said a 50-50 chance of 25 years , which is worlds apart from Rae's misquote.


... and he says a 10% chance of it taking 100 years, and that it's subject to adequate funding. No one is going to build in all the caveats every time they discuss the same projection that's already been explained. Again, you're treating one quote out of a longer talk as all that was presented. Even in the section to which you refer I make additional reference to caveats about funding, and Dr. de Grey himself also presented in the same session as me. No one who was paying any attention would come away with thinking that he or anyone else had put forward a hard 25-year crystal-ball prediction.
 
bluemoon said: By the way, my undergrad degrees are in physics and mathematics - no biologist here! :)  What is your science background, Michael since you implied above that you have a science background of some sort, so can you tell us what it is? I think nothing since high school.

 

It is very hard for me to believe that any fair-minded reader would view the minor error and out-of-context statement you've presented as evidence that I have "no science background," but again: even if I had none, you'd still be attacking the person presenting the argument rather than the argument itself.

 

Not that I should have to say this, but to be clear: I was a biology major in university until my last year, when it became clear that I was never going to make it in the laboratory no matter how good my grades on written exams got, so I changed majors and made biology a minor. And I read scientific literature and interact with scientists almost every day of my life, and have done so for years.


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#1598 prophets

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Posted 27 November 2016 - 12:27 AM

stuff

 

Attack the argument. If you think Michael Rae's argument about NR and cancer are nonsense, then attack the argument about NR/cancer with valid analysis or some kind of informed opinion about NR and cancer.  

 

Don't attack the person.  Don't sit here and give us this song and dance about his lack of credibility, his academic deficits, or how he was wrong 6 years ago about some grandiose-spitball prediction that is unrelated to NR.


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#1599 Bryan_S

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Posted 27 November 2016 - 12:31 AM

And we wonder why people don't like these rants against one another. This is a forum to share and discuss research surrounding NAD repletion. I don't require you to discuss nicotinamide riboside exclusively because it is just one facet of interrelated topics surrounding NAD boosting. But I do require that all members be civil with one another. The way I see the whole picture is that with each study our understanding of aging changes in some way. Lets take for instance the Mitochondrial Theory of Aging. There are researchers challenging the status quo like Professor Hayash.

 

Now we can't keep digging into the record to see if someone was right or not each time the story changes a few degrees. The story of senescence, CD38, PARP, the slow drift of our epigenome are all weighing into the story of aging and all it takes is a small insight to change everything. Any timelines we put forward are useless. All it takes is a paper like this one from Northwestern University and the whole field could take another direction. This paper ties reproductive maturity with epigenetic changes leading to old age.

 

So that being said I don't see NAD repletion as the end story either. Many of our assumptions will inevitably be challenged, some reaffirmed some trashed as these metabolic studies move from animal to human trials. At one point I also had a difference of opinion with Michael and there have been a couple of dozen papers between then and now and to argue a point based on the understanding of that particular day that we've seen redefined since seems a waste of time. So lets all turn off the biased marketing claims from the sidelines, focus on the current research and forget about what someone opinionated yesterday, especially since the pace of change is going to get more rapid.


Edited by Bryan_S, 27 November 2016 - 12:37 AM.

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#1600 Michael

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Posted 27 November 2016 - 12:36 AM

I'd certainly acknowledge that some of the questions and objections I raised in my QOTM post almost exactly a year ago have been addressed in subsequent research. As Midas points out, there's now evidence that NMN can work after oral administration, and the same study reported finding elevated NMN in plasma following oral gavage. A previous study found that "Perfused or intact intestine rapidly hydrolyzed NMN to nicotinamide riboside, which accumulated, but was not absorbed. It was slowly cleaved by an enzyme associated with the mucosal cells to nicotinamide, which was the major if not the only labeled compound absorbed." I assume this is why all of Imai's and Sinclair's studies prior to this new one delivered NMN via injection, which is a lot more troublesome than orally in water or feed: Imai seems to be hinting at just that when he writes, "In our previous study, we showed that a bolus intraperitoneal administration of NMN (500 mg/kg body weight) increased tissue NMN and NAD+ levels within 15 min in the liver, pancreas, and white adipose tissue (WAT) in regular chow-fed wild-type mice (Yoshino et al., 2011). To make long-term NMN administration possible, we decided to test lower doses, which could potentially be translatable to humans, and add it to drinking water."

 

Charles Brenner has recently reported that NR elevates NMN levels in several tissues after oral absorption, and in the process substantially changed our understanding of the metabolism of NAD precursors; he had cited NMN's hydrolysis in the intestine per the earlier study in outlining the proposed route of uptake of NAD precursors from the diet in a review several years back. One way to reconcile these findings is of course that NMN is indeed hydrolyzed to NR in the intestine, but that NR is then taken up and elevates NMN in the blood, though I don't know what explains the finding of non-absorption even of NR in the earlier study.

 

Similarly, several studies have also now reported nicotinamide riboside to elevates NAD in muscle, most importantly Zhang, Auwerx (2016), et. al. discussed above.


Edited by Michael, 27 November 2016 - 12:41 AM.

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#1601 Bryan_S

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Posted 27 November 2016 - 12:50 AM

Michael don't be chased away because all researched opinions are welcomed here. In all honesty I was one of your original critics and may have set the tone here, for that I'm sorry. We are all just trying to take this research in and make sense of it and the rate at which these papers are being published is escalating. So as we sift thru these papers we're hoping to attract some reasoned commentary, so stick around and join the conversation.  :)


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#1602 bluemoon

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Posted 27 November 2016 - 01:58 AM

 

 

(b) The full quote is, "it hasn't been, since 1950, that we've made much change at the far end" (emphasis added). Median LS of course still incorporates ongoing progress in lowering deaths childhood mortality, and "premature" mortality in midlife.

 

 

 

See? I didn't chase Micheal away. What's wrong prophets? I didn't create a safe place for Michael? He isn't 11 years old, right? 

 

Michael, you were simply wrong about what you said then as life expectancy over 65 had increased about 6 or 7 years since 1950 independent of childhood longevity.

 

You also said in your presentation that if a person is 50 today (58 in 2016) than only a third of you are 'going to make it' and added "A lot of you are going to make it as far as 150 years and still cough out - but that ain't bad! But you know what, we don't have a cure today... (so worse odds).

 

You were telling the audience that many of those who "won't make it" (to escape velocity) will live until the year 2108 (!) as if you knew what longevity science would look like in the 22nd century to say nothing of 2070 or 2030. That is the point I rolled my eyes and thought you can't have a science background. But as you wrote, you studied biology for 3 years, so I take that back.

 

As for cheer leading, I clearly stated that is very important. What I wrote: "Rae is a cheerleader, and we need those." I also consider Aubrey de Grey a cheerleader, and a great one for longevity. 

 

Prophets has been full of it - twice. First, I have never gone off topic considering I responded to bold statements that were previously made. Second, I have never attacked a person. To me, saying Michael didn't have any science background seemed obvious from that presentation but I admit I was wrong.

 

以上です。


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#1603 Iporuru

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Posted 27 November 2016 - 09:31 AM

http://www.ebiomedic...0524-2/fulltext

 

Article Outline

 

    1. Introduction

    2. Ageing as a Clinical Indication

    3. Repurposing Drugs to Combat Ageing

        3.1. Rapamycin and mTOR Inhibition

        3.2. TAMEing Ageing With Metformin

        3.3. Second Generation Repurposed Anti-ageing Compounds?

    4. New Compounds Specifically Developed to Target Ageing

        4.1. NAD+ Supplementation

        4.2. Senolytics

    5. Biomarkers for Detecting Drug Efficacy Against Ageing

    6. Conclusions

    7. Outstanding Questions


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#1604 Mike C

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Posted 27 November 2016 - 11:33 PM

WRT MIchael Rae I have been following his posts for 20 years and the attackers have come and gone over the years on the CRsociety as well as this site and Michael just keeps on plugging away. He is not one to be the least bit intimidated by this so I would not get to concerned about it. IAC, his input is certainly one I pay close attention to for the very reasons Sthira has pointed to in his post. Thanks Sthira!
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#1605 Thell

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Posted 28 November 2016 - 06:02 PM

Recent NMN discussion on this thread made me wonder a little bit more about the specifics of NMNAT. While studying I ran across this...

 

NMNAT1 inhibits axon degeneration via blockade of SARM1-mediated NAD+ depletion (October 13, 2016)

Abstract

Overexpression of the NAD+ biosynthetic enzyme NMNAT1 leads to preservation of injured axons. While increased NAD+ or decreased NMN levels are thought to be critical to this process, the mechanism(s) of this axon protection remain obscure. Using steady-state and flux analysis of NAD+ metabolites in healthy and injured mouse dorsal root ganglion axons, we find that rather than altering NAD+ synthesis, NMNAT1 instead blocks the injury-induced, SARM1-dependent NAD+ consumption that is central to axon degeneration.

 

Excerpt

 

...Surprisingly, we find that neither NAD+loss nor NMN accumulation trigger axon degeneration. Instead, both NMNAT1 and NMN deamidase prevent axon degeneration via blocking the injury-induced NAD+ consumption that occurs following activation of the axodestructive molecule SARM1.


→ source (external link)

 

 


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#1606 albedo

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Posted 30 November 2016 - 09:19 AM

Metabolic control of muscle and muscle stem cell function

http://memento.epfl....le-stem-cell-2/



#1607 Bryan_S

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Posted 02 December 2016 - 06:49 PM

Reductive carboxylation is a major metabolic pathway in the retinal pigment epithelium
 
'NAD+ declines with age (47, 51), and supplementation with NAD precursors can delay aging, liver disease, and vascular dysfunction (52–54). NAD+ precursors, such as nicotinamide riboside, can be used safely in humans (55, 56). In the absence of animal models for AMD, our findings highlight the need for clinical trials that evaluate NAD+ precursors for their ability to prevent and treat AMD."
 
Significance
In the vertebrate eye, a monolayer of cells, called the retinal pigment epithelium (RPE), is between the choroidal blood supply and the retina. The RPE provides metabolic support for the retina, including delivery of glucose and other nutrients. Here, we show that reductive carboxylation of α-ketoglutarate, a type of metabolism that supports growth and survival of cancer cells, is a prominent feature of RPE cells. We show that extreme oxidative stress can overwhelm the reductive carboxylation pathway. However, we also found that the RPE can be protected from extreme oxidative stress by supplementation with an NAD+ precursor or α-ketoglutarate.
 
Abstract
The retinal pigment epithelium (RPE) is a monolayer of pigmented cells that requires an active metabolism to maintain outer retinal homeostasis and compensate for oxidative stress. Using 13C metabolic flux analysis in human RPE cells, we found that RPE has an exceptionally high capacity for reductive carboxylation, a metabolic pathway that has recently garnered significant interest because of its role in cancer cell survival. The capacity for reductive carboxylation in RPE exceeds that of all other cells tested, including retina, neural tissue, glial cells, and a cancer cell line. Loss of reductive carboxylation disrupts redox balance and increases RPE sensitivity to oxidative damage, suggesting that deficiencies of reductive carboxylation may contribute to RPE cell death. Supporting reductive carboxylation by supplementation with an NAD+ precursor or its substrate α-ketoglutarate or treatment with a poly(ADP ribose) polymerase inhibitor protects reductive carboxylation and RPE viability from excessive oxidative stress. The ability of these treatments to rescue RPE could be the basis for an effective strategy to treat blinding diseases caused by RPE dysfunction.
 

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#1608 Bryan_S

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Posted 06 December 2016 - 03:23 PM

Pathway linked to slower aging also fuels brain cancer

http://medicalxpress...ging-fuels.html


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#1609 Nate-2004

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Posted 06 December 2016 - 04:07 PM

Pathway linked to slower aging also fuels brain cancer

http://medicalxpress...ging-fuels.html

 

That's terrible. Hopefully none of us have existing tumors. I assume it's fine if you don't. I don't have a history of that kind of cancer in my family.



#1610 midas

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Posted 06 December 2016 - 05:02 PM

 

Pathway linked to slower aging also fuels brain cancer

http://medicalxpress...ging-fuels.html

 

That's terrible. Hopefully none of us have existing tumors. I assume it's fine if you don't. I don't have a history of that kind of cancer in my family.

 

Scientists Find Promising New Approach to Preventing Progression of Breast Cancer

https://www.scripps....25/felding.html

"To find out if the balance of NAD+ and NADH was critical for tumor cell behavior, the team proceeded to insert a yeast gene into cancer cells that caused a shift toward more NAD+. To the scientists’ amazement, this shift caused the tumor cells to become less aggressive.

“It was a really happy moment for me,” said Santidrian. But the more exciting moments, he said, were yet to come.

To confirm and extend the initial findings, the team altered genes tied to NAD+ production. The resulting shift again showed that higher NADH levels meant more aggressive tumors, while increased NAD+ had the opposite effect.

The next logical step was to find a simple way to enhance the critical NAD+ level therapeutically. So the team explored what would happen if mice with breast cancer were fed water spiked with nicotinamide, a precursor for NAD+ production. The scientists found cancer development was dramatically slowed down, and the mice lived longer

“In animal models at various stages, we see that we can actually prevent progression of the disease,” said Felding."

 

_____________________________________________________________________________________________________

 

According to this, if I am reading it properly, NAD can be a preventer and also under certain circumstances helper of cancer. It seems it can help cancer along in later stages and be peventative by keeping cells healthy pr-cancer... Also, Glioblastomas mentioned in the link in Bryan's post are usually found at the later stage of the disease rather than at the early stages.

 

http://www.scitechno...article_id=5285


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#1611 lumia

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Posted 07 December 2016 - 02:01 AM

 

Pathway linked to slower aging also fuels brain cancer

http://medicalxpress...ging-fuels.html

 

That's terrible. Hopefully none of us have existing tumors. I assume it's fine if you don't. I don't have a history of that kind of cancer in my family.

 

 

One of my grandfathers and his sibling died of brain cancer. Don't know which type. I don't know what this means anymore.


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#1612 Harkijn

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Posted 07 December 2016 - 08:48 AM

 

 

Pathway linked to slower aging also fuels brain cancer

http://medicalxpress...ging-fuels.html

 

That's terrible. Hopefully none of us have existing tumors. I assume it's fine if you don't. I don't have a history of that kind of cancer in my family.

 

 

One of my grandfathers and his sibling died of brain cancer. Don't know which type. I don't know what this means anymore.

 

I think there is reason for some concern and that concern is wider than gioblastoma only. For their in vitro study, the researchers chose glioblastoma cells but we can assume that NAMPT works similarly in other cancers. This risk is not a totally novel finding, for the Aging Firewalls blog has extensively written about the dual nature of NAMPT. I am glad that results of human NR trials will be in rather soon.


Edited by harkijn, 07 December 2016 - 08:48 AM.


#1613 midas

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Posted 07 December 2016 - 12:12 PM

I pointed this out a week or two ago......Keep in mind that the majority of cancers in later life and NAD declines with age. So, if NAD was such a big deal when it comes to cancer wouldn't that mean we were more susceptible to cancers when our NAD pool was full rather than when its running low.


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#1614 Daniel Cooper

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Posted 07 December 2016 - 02:56 PM

So at this point the summary seems to be that higher NAD+ levels are unlikely to cause you to develop cancer and in fact my offer some protection against the formation of cancerous cells, but once you actually get cancer higher NAD+ levels may cause come cancers to become more aggressive (e.g. glioblastoma) but may have the opposite effect on others (e.g. breast cancer).

 

If so, it this makes determining what to do with regards to NR supplementation very murky indeed.  None of us has a crystal ball to see what types of cancer we will ultimately develop.  I have suspended my NR supplementation for other reasons but have intended to restart it in a few months.  Now I'm not so sure.  This would seem to merit more study and some caution.  I can certainly say that if I had relatives that developed glioblastoma I would be very reluctant to supplement with NR at this time, but even that position has it's difficulty as glioblastoma is not currently thought to be strongly tied to heredity.

 

 



#1615 Daniel Cooper

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Posted 07 December 2016 - 03:26 PM

So let's take the assumption I made above, i.e. that increased levels of NAD+ don't generally cause cancer, but they can fuel some cancers once they develop, glioblastoma in particular.

 

That assumption would probably lead you predict that children (which have higher NAD+ levels) which develop glioblastoma would have a worse prognosis than those that develop glioblastoma at middle age or later.

 

However, that doesn't seem to be the case.  

 

Long-term outcomes in children with glioblastoma     https://www.ncbi.nlm...pubmed/20672935

 

Of course, we're trying to look a single variable here in isolation, which we can't do.  Perhaps a child's immune system is a bit more successful at fighting glioblastoma than someone in middle age.  Or it could be one of any numbers of other differences in a child versus an adult that overcome to some extent the tendency for higher levels of NAD+ to fuel glioblastoma.

 

 

 

 


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#1616 Harkijn

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Posted 07 December 2016 - 04:20 PM

Valid points Midas and Daniel, though I am not totally reassured yet. Meanwhile I am happy that this press release just reached me.

 

 https://www.elysiumh...l-press-release


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#1617 Daniel Cooper

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Posted 07 December 2016 - 04:31 PM

Valid points Midas and Daniel, though I am not totally reassured yet. Meanwhile I am happy that this press release just reached me.

 

 https://www.elysiumh...l-press-release

 

 

Oh believe me, I am by no means reassured.  In fact I have to be careful in my evaluation of this given how badly I don't want this to be a problem with NR.  At this point all I see is murkiness, and the study on glioblastoma in children vs adults is by no means any sort of definitive answer.  It's really only an indication of how inadequate our knowledge is on NR vs. cancer promotion.

 

 

What we really need is a mouse model for glioblastoma (does one exist?) and then feed a control and study group NR and see what happens.

 

 


Edited by Daniel Cooper, 07 December 2016 - 04:35 PM.

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#1618 Thell

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Posted 07 December 2016 - 04:42 PM

Valid points Midas and Daniel, though I am not totally reassured yet. Meanwhile I am happy that this press release just reached me.

 

 https://www.elysiumh...l-press-release

 

We've been waiting to hear some results information (let alone the study publication) so this is indeed a happy occasion.

 

A quote to those involved in the 'max' NAD+ level discussion a few pages back...

 

 

The study, which was placebo-controlled, randomized, and double-blinded, evaluated the safety and efficacy of BASIS™ [nicotinamide riboside (NR) and pterostilbene] in 120 healthy participants ages 60-80 over an eight-week period. Participants received either the recommended dose (250 mg NR and 50 mg pterostilbene), double the recommended dose or a placebo daily for the eight-week trial.

The study found that participants experienced no serious adverse events and confirmed that BASIS™ is safe for daily use as determined by standard safety measures. The study also showed that in participants taking the recommended dose of BASIS, ™ NAD+ levels increased from baseline in whole blood by an average of 40% at four weeks and maintained that increase for the duration of the trial. Participants taking double the recommended daily dose saw their NAD+ levels increase approximately 90% at four weeks, and a significantly higher level of NAD+ (compared to the recommended dose of BASIS™) was maintained for the duration of the trial. This first-in-humans study demonstrates clearly that BASIS™ can increase NAD+ levels in the blood safely and sustainably. Confirming that BASIS™ is an effective NAD+ precursor in humans is a vital first step to elucidating how BASIS™ supports human health.

 

Can't wait to read the study!


Edited by Thell, 07 December 2016 - 04:43 PM.

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#1619 bluemoon

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Posted 07 December 2016 - 05:10 PM

 

Can't wait to read the study!

 

 

But how long for the wait? Late next year, right?



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#1620 Anthony_Loera

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Posted 07 December 2016 - 05:28 PM

 

Valid points Midas and Daniel, though I am not totally reassured yet. Meanwhile I am happy that this press release just reached me.

 

 https://www.elysiumh...l-press-release

 

We've been waiting to hear some results information (let alone the study publication) so this is indeed a happy occasion.

 

A quote to those involved in the 'max' NAD+ level discussion a few pages back...

 

 

The study, which was placebo-controlled, randomized, and double-blinded, evaluated the safety and efficacy of BASIS™ [nicotinamide riboside (NR) and pterostilbene] in 120 healthy participants ages 60-80 over an eight-week period. Participants received either the recommended dose (250 mg NR and 50 mg pterostilbene), double the recommended dose or a placebo daily for the eight-week trial.

The study found that participants experienced no serious adverse events and confirmed that BASIS™ is safe for daily use as determined by standard safety measures. The study also showed that in participants taking the recommended dose of BASIS, ™ NAD+ levels increased from baseline in whole blood by an average of 40% at four weeks and maintained that increase for the duration of the trial. Participants taking double the recommended daily dose saw their NAD+ levels increase approximately 90% at four weeks, and a significantly higher level of NAD+ (compared to the recommended dose of BASIS™) was maintained for the duration of the trial. This first-in-humans study demonstrates clearly that BASIS™ can increase NAD+ levels in the blood safely and sustainably. Confirming that BASIS™ is an effective NAD+ precursor in humans is a vital first step to elucidating how BASIS™ supports human health.

 

Can't wait to read the study!

 

 

Well this is some good news Thell,

 

Thanks for sharing.

A


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