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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 midas

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Posted 22 November 2016 - 10:24 PM

However, it should be pointed out that one study found that NR supplementation decreased exercise performance in normal rats by 35% (Kourtzidis et al., 2016recycling (see image 2) (Frederick et al., 2016). However, it should be pointed out that one study found that NR supplementation decreased exercise performance in normal rats by 35% (Kourtzidis et al., 2016

That study should be replicated because that is very negative if true! Exercise capacity is vigoursley, pun intended, associated with health/longevity. Anything that diminishes that is something I want no parts of!!!

 

That review is very scrappy anyway.......Who wrote that!.....

 

The fact that this is included when it has been tested to be safe in humans is a little over the top if you ask me....."Also the reduced exercise performance in rats fed NR is a warning that we shouldn’t implement NR supplementation in healthy humans as of yet"

 

There are plenty of people taking NR and I think one thing you will find is that no one has complained about reduced exercise ability... I have more energy now than I had before taking NR so it's quite the opposite for me.


Edited by midas, 22 November 2016 - 10:31 PM.

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#1592 Bryan_S

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Posted 23 November 2016 - 04:14 AM

However, it should be pointed out that one study found that NR supplementation decreased exercise performance in normal rats by 35% (Kourtzidis et al., 2016recycling (see image 2) (Frederick et al., 2016). However, it should be pointed out that one study found that NR supplementation decreased exercise performance in normal rats by 35% (Kourtzidis et al., 2016

That study should be replicated because that is very negative if true! Exercise capacity is vigoursley, pun intended, associated with health/longevity. Anything that diminishes that is something I want no parts of!!!

 

http://jissn.biomedc...2970-016-0143-x

 

Lets just say the study was a little underfunded and largely ignored.

http://www.longecity...-35#entry784963

 

On rats, lets see what happens with humans. Here is where the experiment got replicated, it should be wrapping up soon.

Thorne Research Announces Clinical Study to Assess Nicotinamide Riboside on Brain NAD+ in College Football Players


Edited by Bryan_S, 23 November 2016 - 04:19 AM.

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#1593 Anthony_Loera

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Posted 23 November 2016 - 07:45 PM

Hi Bryan,

 

You and richard hnry posted this on another thread:

http://www.cell.com/...1247(15)01347-9

 

If we were zebra fish, would you think NR might also have issues with this neural degeneration syndrome?

 

I am just asking because of how NMN is related, 

 

[update]

 

From your interview here, it might be an issue with NR as well... (See minute 15, 58 seconds)

https://youtu.be/WItMH3PzIk4?t=15m58s

 

A


Edited by Anthony_Loera, 23 November 2016 - 08:14 PM.

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#1594 Anthony_Loera

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Posted 23 November 2016 - 07:50 PM

I've been a long time lurker on this thread, I get email updates for every post and I've followed this topic closely.
I want to give Kudo's to Bryan. What he's doing isn't easy. I for one get annoyed with those that continually try to hijack the thread with their own pet topics. He's done a fair and necessary job as moderator.
Start your own thread topic f you don't like Bryan's focus.
I've been taking 500 mg per day in divided doses. I altered my intake to 250mg twice a day after watching Bryan's interview.
Ok, all that being said I'll go back to reading to the updates unless I have something useful to add......

 

 

That sounds interesting...

can you provide a link to Bryans interview?

 

I have been away for a while, and would like to check it out.

A



#1595 Anthony_Loera

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Posted 23 November 2016 - 07:57 PM

Is this the one? Thanks

 

A



#1596 Michael

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Posted 24 November 2016 - 08:30 PM

All:
 

(Pardon the hash created by the Forum's ridiculous quote-function restrictions below...)

 

Michael Rae ... only believes in CR as an anti aging protocol.


That is, of course, untrue. Lots of things work as anti-aging therapies in rodents (rapamycin, CR, true methionine restriction, various mutations in the IGF-1 pathway,  SIRT6 overexpression, etc); unfortunately, most of them are not practicable by humans. If we're talking about things that are both reasonably well-supported as anti-aging interventions in other mammalian species and practicable by humans, then certainly the case is strongest for CR (tho' even there, saying that I "believe in it" is an overstatement of my confidence), but rapamycin is very promising if we can identify a dose that is both reasonably safe and effective, and there's reason for optimism on a few other drugs and supplements.
 
Kevnzworld said: Michael Rae is biased. ... He dismisses research that doesn't fit his world view.

No, I dismiss conclusions drawn from research that is claimed to show things it doesn't show. Most notably, I dismiss the imputation of anti-aging effects to compounds based on lifespan studies carried out in obese and/or diabetic and/or mutant and/or toxin-administered and/or poorly-husbanded animals with abnormally short baseline lifespan. Again: the historical benchmark for lifespan in genetically normal, well-nourished, nonobese, well-cared-for laboratory mice is ≈850 d mean and ~1100 d max (10th-decile survivorship). The fact that some compound partially normalizes the lifespan of animals that for whatever reason lives an abnormally-short life to  begin with in no way validates it as an anti-aging therapy. Gleevec and combination antiretroviral therapies have dramatically increased the life expectancies of CML and HIV/AIDS patients (respectively) is not evidence that they should be taken by healthy normal people for life extension.
 
Kevnzworld said: The study that showed that diabetic people on Metformin outlived non diabetics being one example.

That study is flawed, as Prophets (and, prior to him, I) have pointed out. Meanwhile, metformin has been found not to extend lifespan in normal, well-fed, nonobese, well-cared-for, non-genetically-FUBARed rodents in four separate lifespan studies carried out in seven separate expert labs, a randomized clinical trial (not flawed epidemiology) has found that metformin is of little benefit in nondiabetic humans at high cardiovascular risk, and metformin is inferior to modest diet and exercise changes in people with elevated fasting glucose or impaired glucose tolerance.

Kevnzworld said: He has not read or studied the research on NR/NAD .
 
I'm not sure where you got that impression; it's mistaken, as Prophets has already pointed out.
 

Michael Rae is certainly very opinionated.  He has a very strong view of CR vs. "everything else", but he seems pretty data driven.  His opinions aren't without merit.  In a message forum full of incomplete information and an Internet full of hucksters pushing supplements, I think his thought process is excellent, even if he seems somewhat close minded on non-CR interventions given the high threshold of "proof" he seems to require.


I think that's reasonably fair, though there's an obvious conflict between the perception that I "seem somewhat close-minded on non-CR interventions" and noting the "high threshold of "proof" [' I would say "evidence"]" I require to take something seriously as a potential anti-aging intervention. And actually, I don't think my evidentiary threshold is all that high: it's just that the evidentiary threshold accepted by life extension hopefuls is often low, or they aren't aware that their own standards aren't being met.
 
Prophets said: It'd be interesting to see if he had updated thoughts and was following some of the more recent publications like Zhang, Auwerx (2016), et. al. that seem to indicate life extension properties.
 
krwBVJi.png


Attentive readers will already have guessed what I'm going to point out here. While there was a nominal difference between the two groups' median lifespans, both groups' median lifespans were still well within the normal zone for healthy mice. The authors don't report maximum (tenth-decile) survivorship, an increase in which relative to normal, healthy controls is the sine qua non of an anti-aging intervention, but you can see right from the survival curves that this doesn't cut it: the very last control animal died at age ≈960 days (700 days (see legend to Figure 6) + an eyeballed 260 d from the graph)), and the last treated animal died at age ≈1010 days: ie, the controls were abnormally short-lived, and the treated animals on the low side of normal. This is already clear just from looking at the shape of the survival curve itself, which is clearly not rectangular: from ≈850 days onward, both groups were clearly suffering abnormal early attrition. It would have been nice to have been able to see the survival curves throughout the adult LS instead of just from initiation of treatment.


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#1597 bluemoon

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Posted 26 November 2016 - 12:17 AM

I watched Michael in a 2008 TED talk and thought  he was 1) a zealot about CR and 2) sloppy at times. He works for Aubrey de Gray but said that de Gray said "escape velocity is 25 years away". No, De Gray said he thought there was a 50-50 chance that it was 25 years away, which is a huge difference. OK, a slip, but he was making a dramatic point to the audience how almost no one will "make it." So he should at least have his facts straight about what his guru said.

 

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


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#1598 Michael

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Posted 26 November 2016 - 12:48 AM

All:
 
Here's a great party trick: run into an argument whose conclusions you don't like, but against which you have no counterargument? No problem! Ignore the argument, and attack the person making it.
 

I watched Michael in a 2008 TED talk


That's a pretty neat trick, since I've never done a TED talk. I suspect you're thinking of the few minutes of non-contiguous excerpts from a 2008 IdeaCity presentation I did that are available online, since IdeaCity loosely resembles the TED format.
 

I and thought  he was 1) a zealot about CR and 2) sloppy at times. He works for Aubrey de Gray


You mean, when attended the wrong event, I also misspelled the name of my boss? That's pretty sloppy, I have to agree.
 

but said that de Gray said "escape velocity is 25 years away". No, De Gray said he thought there was a 50-50 chance that it was 25 years away, which is a huge difference.


I explain this to people literally about once a week, as well as the fact that even that is contingent on still-forthcoming funding. Again, you're jumping to conclusions as a result of lacking context, having seen only short excerpts from my talk.
 

OK, a slip, but he was making a dramatic point to the audience how almost no one will "make it." So he should at least have his facts straight about what his guru said.

 
First, again you're just mistaken in thinking that I firmly asserted a hard 25-year takeoff timeline. But in any case, if you think about this for even half a second, you'll realize that that would be self-defeating, not clever rhetoric: the earlier I suggest Escape Velocity will arrive, the less imperative it is to gain a slow-aging advantage to make the cut.
 
Bluemoon said: Michael has no science background whatsoever, and that should be kept in mind. Rae is a cheerleader, and we need those.

I have no experience as a working bench scientist, because I discovered early on that I'm no better in the lab than I am at home renovation. That's hardly the same thing as having "no science background whatsoever," and it has no relevance to the soundness of my arguments.


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#1599 bluemoon

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Posted 26 November 2016 - 04:07 AM

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. 

 

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.   

 

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.

 

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.

 

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

 


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#1600 midas

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Posted 26 November 2016 - 07:49 PM

Metabolic control of muscle and muscle stem cell function

 

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


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#1601 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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#1602 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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#1603 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/

 

 

------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------



(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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#1604 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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#1605 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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#1606 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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#1607 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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#1608 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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#1609 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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#1610 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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#1611 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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#1612 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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#1613 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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#1614 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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#1615 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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#1616 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/



#1617 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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#1618 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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#1619 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.



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#1620 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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