"An unexpected function of the oxidized form of nicotinamide adenine dinucleotide (NAD+) could underlie some effects of aging and propensity to age-related diseases. Li et al. found that the protein DBC1 (deleted in breast cancer 1) contains a domain that specifically binds NAD+. Binding of NAD+ inhibited the interaction of DBC1 with PARP1 [poly(adenosine diphosphate–ribose) polymerase 1], an enzyme important in DNA repair. Activity of PARP1 is inhibited by interaction with DBC1. Thus, the reduced abundance of NAD+ associated with aging may decrease PARP1 activity by promoting the interaction of PARP1 with DBC1. This mechanism could help explain the reported rejuvenating actions of NAD+ supplementation in older animals."
"An unexpected function of the oxidized form of nicotinamide adenine dinucleotide (NAD+) could underlie some effects of aging and propensity to age-related diseases. Li et al. found that the protein DBC1 (deleted in breast cancer 1) contains a domain that specifically binds NAD+. Binding of NAD+ inhibited the interaction of DBC1 with PARP1 [poly(adenosine diphosphate–ribose) polymerase 1], an enzyme important in DNA repair. Activity of PARP1 is inhibited by interaction with DBC1. Thus, the reduced abundance of NAD+ associated with aging may decrease PARP1 activity by promoting the interaction of PARP1 with DBC1. This mechanism could help explain the reported rejuvenating actions of NAD+ supplementation in older animals."
"Human trials with NMN therapy will begin within six months" at Brigham and Women's Hospital in Boston.
Indeed, I believe the "discovery" happened few years back. Only more elaborate theory now how it works? A new paper for similar content, similar experiment.... This happens a lot to nowadays professors...keep publishing the same content (twisting a bit only) on several journals/conferences...
"An unexpected function of the oxidized form of nicotinamide adenine dinucleotide (NAD+) could underlie some effects of aging and propensity to age-related diseases. Li et al. found that the protein DBC1 (deleted in breast cancer 1) contains a domain that specifically binds NAD+. Binding of NAD+ inhibited the interaction of DBC1 with PARP1 [poly(adenosine diphosphate–ribose) polymerase 1], an enzyme important in DNA repair. Activity of PARP1 is inhibited by interaction with DBC1. Thus, the reduced abundance of NAD+ associated with aging may decrease PARP1 activity by promoting the interaction of PARP1 with DBC1. This mechanism could help explain the reported rejuvenating actions of NAD+ supplementation in older animals."
A question to those who are able to read the data in this study: at first the researchers compared the effects of NMN as well as NR.
Then they hypothesize that ' a cause (of aging) may be increased binding of DBC1 to PARP1 as NAD+ levels decline during aging. To test this, we examined the effect of NMN treatment on young and old mice.'
They do not motivate their decision to choose for testing with NMN and not with NR. Is there anything in the data that makes it obvious to choose for NMN?
"They do not motivate their decision to choose for testing with NMN and not with NR. Is there anything in the data that makes it obvious to choose for NMN?"
If I'm Sinclair, I will also choose NMN, Sinclair wont make a dime if NR sells more because of this experiment!
"They do not motivate their decision to choose for testing with NMN and not with NR. Is there anything in the data that makes it obvious to choose for NMN?"
If I'm Sinclair, I will also choose NMN, Sinclair wont make a dime if NR sells more because of this experiment!
You certainly have a point but it is not the whole picture. If this group had wanted to 'boycot' NR, they would not have used it at all in the first place. So my question remains valid: is there anything in this research that makes NMN the logical choice above NR for testing and replication?
"They do not motivate their decision to choose for testing with NMN and not with NR. Is there anything in the data that makes it obvious to choose for NMN?"
If I'm Sinclair, I will also choose NMN, Sinclair wont make a dime if NR sells more because of this experiment!
You certainly have a point but it is not the whole picture. If this group had wanted to 'boycot' NR, they would not have used it at all in the first place. So my question remains valid: is there anything in this research that makes NMN the logical choice above NR for testing and replication?
concentration: 500 mg/kg per day intraperitoneally
The Daily Mail has an exclusive story about Sinclair's NMN trial. Sensational as usual.
Would YOU choose to live forever? Age-reversing pill that Nasa wants to give to astronauts on Mars will begin human trials within six months
The experiments in mice, from a team at the University of New South Wales, suggest a treatment is possible for DNA damage from ageing and radiation.
It is so promising it has attracted the attention of Nasa scientists in their quest to reach Mars.
While our cells can naturally repair DNA damage - such as damage caused by the sun - this ability declines with age.
The scientists identified that the call signalling molecule NAD+, which is naturally present in every cell in the body, has a key role in protein interactions that control DNA repair.
Treating mice with an NAD+ 'booster' called NMN improved their cells' ability to repair DNA damage caused by radiation exposure or old age.
Human trials of NMN therapy will begin within six months.
"They do not motivate their decision to choose for testing with NMN and not with NR. Is there anything in the data that makes it obvious to choose for NMN?"
If I'm Sinclair, I will also choose NMN, Sinclair wont make a dime if NR sells more because of this experiment!
You certainly have a point but it is not the whole picture. If this group had wanted to 'boycot' NR, they would not have used it at all in the first place. So my question remains valid: is there anything in this research that makes NMN the logical choice above NR for testing and replication?
concentration: 500 mg/kg per day intraperitoneally
After that they switched to feeding mice NMN in their drinking water and after only one week(!) drastic changes were measured.
It's easier to make big changes in short-lived rodents. Were these genetically modified rodents? And these rodents were given 500 mg per kg?
So for me, I'm 70 kg, that's 35,000/mg per day of (Niagen). 280 pills per day (125/mg per pill). A bottle of 90 pills is currently $78.99 on Amazon. So every day (for how long?) I'd need to take three bottles of Niagen pills, or $237.00 per day?
So we think, ok, these are our lives, our health, and we want to be amazing like NASA astronauts headed off into profound space radiation on mission to Mars; so is spending $86,000 per year the price we pay (assuming mice studies translate to human studies)? Which, btw, was there a small, ten-person human trial regarding NR in Japan last summer?
It's easier to make big changes in short-lived rodents. Were these genetically modified rodents? And these rodents were given 500 mg per kg?
So for me, I'm 70 kg, that's 35,000/mg per day of (Niagen). 280 pills per day (125/mg per pill). A bottle of 90 pills is currently $78.99 on Amazon. So every day (for how long?) I'd need to take three bottles of Niagen pills, or $237.00 per day?
So we think, ok, these are our lives, our health, and we want to be amazing like NASA astronauts headed off into profound space radiation on mission to Mars; so is spending $86,000 per year the price we pay (assuming mice studies translate to human studies)? Which, btw, was there a small, ten-person human trial regarding NR in Japan last summer?
I am sure you have heard already about allometric scaling.
I didn't see anything new it's just pure sensationalism. Sinclair just seemed to be beating the drums on the NMN bandwagon, and his timing was impeccable. He's rather good at this kind of fluff, attracting research dollars.
What's new is the idea involving space travel to Mars with President Trump's announcement. I'm sure for Sinclair the blinking lights, sirens and alarms went off; there are real research dollars to be had to prove NAD Repletion does work.
So when Michael E. Salla's article hit, NMN and DNA repair didn't arouse a lot of serious interest, but with the research-home-runs with nicotinamide riboside and earnest University study, it's a new game.
So if you want a real big grin See: http://exopolitics.o...cally-feasible/ but while you are $miling remember there is real money out there to be grabbed.
We can spin all the same claims for nicotinamide riboside. If Dr. Brenner monitors our thread, I think "today" is the day to pitch a research grant on "repairing DNA from ionizing particle radiation while in space." In fact, I'd like a piece of that and will gladly help tell the story with video support.
I still don't see any advantage to switching from NR to NMN. Unless it's cheaper or does something that nicotinamide riboside can't. So if you put me on a spaceship today, I'd carry plenty of NR for the round trip.
Here is a video of a "Wilson cloud chamber" showing the normal radiation at sea level and at altitude. Exposure is inevitable for everyone, we've evolved the tools to repair the damage. It's a part of living on spaceship Earth and more intense in a tiny tin can traveling in space.
As always JMHO
We've posted it before but no problem. Try running the study title in the search field in the top right of this web-page if you're not sure.
There has been a considerable amount of research on NMN. Even if it has to be converted to NR to cross the cell membrane, if it can be stabilized and encapsulated and priced below NR we might see a product emerge. So far however there has been no such "verifiable" product. Still every NAD+ boosting study contributes to our knowledge base. However I feel since NR and NMN bypass the de novo NAD path and cut in line, I would think their study results would be almost identical if they were examined side by side. NR might win out just from a pure efficiency standpoint but NMN is going to trail in a close 2nd.
i.e. "no such "verifiable" product" thats changed.
NMN β-Nicotinamide mono nucleotide buy which is exorbitantly priced and not at all competitively priced to (NR). But if you believe the hype, they say its better than (NR), so be my guest if you agree. However beware of the www.alibaba.com offers and the companies repackaging the Chinese products because independent testing is lacking.
Now here is an "off the wall" article that comes to us from the fringe that was just posted. AGE REGRESSION USED IN SECRET SPACE PROGRAMS CONFIRMED AS SCIENTIFICALLY FEASIBLE. Now while I don't see enough evidence to buy the ideas thrown about here, I do see where a correlation might exist in the area of repairing DNA from ionizing particle radiation while in space. These guys who put only a millimeter of aluminum between themselves and space are receiving a lot more DNA damage than we do. These guys deserve respect! Examples of ionizing radiation include gamma rays, protons, and neutrons. So I think if NASA medical scientists have been paying attention I would think the mounting NAD+ boosting evidence should have been applied if it hasn't all ready for those who expose themselves to the harshest of DNA damaging environments.
It's easier to make big changes in short-lived rodents. Were these genetically modified rodents? And these rodents were given 500 mg per kg?
So for me, I'm 70 kg, that's 35,000/mg per day of (Niagen). 280 pills per day (125/mg per pill). A bottle of 90 pills is currently $78.99 on Amazon. So every day (for how long?) I'd need to take three bottles of Niagen pills, or $237.00 per day?
I do see where a correlation might exist in the area of repairing DNA from ionizing particle radiation while in space. These guys who put only a millimeter of aluminum between themselves and space are receiving a lot more DNA damage than we do. These guys deserve respect! Examples of ionizing radiation include gamma rays, protons, and neutrons. So I think if NASA medical scientists have been paying attention I would think the mounting NAD+ boosting evidence should have been applied if it hasn't all ready for those who expose themselves to the harshest of DNA damaging environments.
Astronauts are grounded by NASA once their lifetime risk of cancer increases to 3%. Also, any cancer except of the thyroid, shows up around 30 years later and there will very likely be a cure by 2037 for those astronauts who have already been fllying for ten years.
The trial that will start in six months is a drug based on NMN, not just NMN, right?
The trial that will start in six months is a drug based on NMN, not just NMN, right?
For DNA repair I think any NAD precursor would be useful in this regard. So NR or NMN likely makes no difference. Someone would have to do a comparative study.
One of the articles that covered this incorrectly stated that Sinclair has created a drug called 'NMN.' The article above wasn't clear if Sinclair's drug in 3 to 5 years is just NMN as Chromadex cells NR under patents, or is it a synthetic drug that will need FDA approval.
Also, I don't think the U of Keio-U of Washington St. Louis study is not the same as the one Sinclair is starting in a Boston hospital in 6 months.
One of the articles that covered this incorrectly stated that Sinclair has created a drug called 'NMN.' The article above wasn't clear if Sinclair's drug in 3 to 5 years is just NMN as Chromadex cells NR under patents, or is it a synthetic drug that will need FDA approval.
Also, I don't think the U of Keio-U of Washington St. Louis study is not the same as the one Sinclair is starting in a Boston hospital in 6 months.
Some of these publications think these molecules are drugs. I didn't read about a drug reference. Sinclair found that PARP1 and DBC1 molecules were binding together and NAD halted or slowed this activity increasing DNA repair because the PARP1 wasn't bound up. "This is a valuable insight" but NR would do the trick just as well since NMN gets reduced to NR to cross the cell membrane anyway.
I see nothing wrong with competition and there is still a lot more to learn and more headlines to come. Let's keep in mind Sinclair is the spin-master, look what he sold to GlaxoSmithKline. That one kind of cratered "GlaxoSmithKline Shuts Down Sirtris, Five Years After $720M Buyout."
As pointed out, it will likely be a few years before the drug Sinclair is developing even becomes available, while NR is available now, no RX required. A few years of NAD boosting in the meantime sounds good to me. Also, despite the cost of supplementing with NR, the price seems to have moderated, and you can bet it's a heck of a lot cheaper than any prescription drug will be, if you can even get it. By the time his product gets approval, there is a definite prospect of further breakthroughs given the momentum that seems to be building in this field.
I see nothing wrong with competition and there is still a lot more to learn and more headlines to come. Let's keep in mind Sinclair is the spin-master, look what he sold to GlaxoSmithKline. That one kind of cratered "GlaxoSmithKline Shuts Down Sirtris, Five Years After $720M Buyout."
The shut down of Sitris was a reorganization but SRT 2401 has been in human trials, one on treating pserosis orally, since then. Which of his studies are flawed or fradulent?
In Science Daily, Sinclair is quoted: "This is the closest we are to a safe and effective anti-ageing drug that's perhaps only three to five years away from being on the market if the trials go well," says Sinclair, who maintains a lab at UNSW in Sydney.
An outlet called TruNews which is reporting on The Daily Mail story included:
Professor Sinclair and Dr. Wu, through their companies MetroBiotech NSW and MetroBiotech International, have worked tirelessly since 2013 to turn NAD+ into a synthesized consumable drug which they have named “NMN”.
During test trials on mice, Professor Sinclair’s team found that their “NAD+ booster” NMN improved the mammals cell ability to repair DNA damage caused by radiation exposure and aging.
“The cells of the old mice were indistinguishable from the young mice after just one week of treatment,” Professor Sinclair told the Daily Mail.
The first human trials will begin in the fall of 2017 at Brigham and Women's Hospital, in Boston.
I see nothing wrong with competition and there is still a lot more to learn and more headlines to come. Let's keep in mind Sinclair is the spin-master, look what he sold to GlaxoSmithKline. That one kind of cratered "GlaxoSmithKline Shuts Down Sirtris, Five Years After $720M Buyout."
The shut down of Sitris was a reorganization but SRT 2401 has been in human trials, one on treating pserosis orally, since then. Which of his studies are flawed or fradulent?
In Science Daily, Sinclair is quoted: "This is the closest we are to a safe and effective anti-ageing drug that's perhaps only three to five years away from being on the market if the trials go well," says Sinclair, who maintains a lab at UNSW in Sydney.
An outlet called TruNews which is reporting on The Daily Mail story included:
Professor Sinclair and Dr. Wu, through their companies MetroBiotech NSW and MetroBiotech International, have worked tirelessly since 2013 to turn NAD+ into a synthesized consumable drug which they have named “NMN”.
During test trials on mice, Professor Sinclair’s team found that their “NAD+ booster” NMN improved the mammals cell ability to repair DNA damage caused by radiation exposure and aging.
“The cells of the old mice were indistinguishable from the young mice after just one week of treatment,” Professor Sinclair told the Daily Mail.
The first human trials will begin in the fall of 2017 at Brigham and Women's Hospital, in Boston.
You take my post the wrong way. I don't take anything away from Sinclair but he is the spin master. I didn't imply he was flawed or fraudulent. Look both sides of this ride on each others coat tales. He plays the press perhaps better than anyone in the field. So a tip of the hat to him.
Working in the media I can tell you he is one of the most polished interviewee's I've seen in awhile.
The Psoriasis angle is something I didn't know about SRT 2401, pretty neat. But we have to admit sirtuins are just one aspect of the equation. An important part by all indicators but raising NAD itself stimulates the sirtuins better than anything else.
Now I like competition but I really don't see any difference in what NMN and NR can do. At this point in time without any comparative data suggesting one is better than the other I see a draw or tie as to the effectiveness of either. NMN still needs to be broken down to NR to be absorbed at the cell membrane.
So from the sidelines where we sit I'm cheering both sides and like competition. A lot of whats going on at the moment however is who can attract the most grant money and who's NAD precursor molecule will dominate the globe. I think this is a win win for us as consumers.
Can someone tell me which one is better based on the picture shown? I really have no idea what those colour/darkness/thickness/whatever indicates. The way I see it is both NMN and NR almost haver the same thickness. Please explain what the picture shows?
"They do not motivate their decision to choose for testing with NMN and not with NR. Is there anything in the data that makes it obvious to choose for NMN?"
If I'm Sinclair, I will also choose NMN, Sinclair wont make a dime if NR sells more because of this experiment!
You certainly have a point but it is not the whole picture. If this group had wanted to 'boycot' NR, they would not have used it at all in the first place. So my question remains valid: is there anything in this research that makes NMN the logical choice above NR for testing and replication?
I guess is that initially they want to prove NMN is far superior than NR, thus included NR in their experiment. However, after the experiment, the results shows that NMN and NR have insignificant differences. They include NR in the report because since they have also tested NR in their experiment, it is not professional not to report that (since the experiment may carry by many people...). And subsequently they abandon NR in all the test. Purely 100% based on my guess work.
"Human trials with NMN therapy will begin within six months" at Brigham and Women's Hospital in Boston.
The new discovery is the mechanism of NAD+ facilitating PARP1-mediated DNA repair in an SIRT1-independent manner, via this newly-discovered abrogation of DBC1 binding.
NMN vs NR, from Sinclair's latest paper:
[Western blots]
Can someone tell me which one is better based on the picture shown? I really have no idea what those colour/darkness/thickness/whatever indicates. The way I see it is both NMN and NR almost haver the same thickness. Please explain what the picture shows?
This picture doesn't tell you anything about that: it's saying that both are, in themselves, completely ineffective. What they're showing here is that the disruption of DBC1 binding to PARP1 is specific to NAD+ itself: it isn't replicated by NMN or NR, and is only very weakly replicated by NADH (as shown by the amount of blotting of DBC1-bound PARP1 in the first lane for each variant of DBC1). Read the paragraph starting "The PARP1-DBC1 complex was abrogated by" etc (second column, first page). Any effect of NMN or NR is thus mediated by its conversion to NAD+; they didn't do any comparative tests of one vs. the other on that basis, opting instead to carry out the rest of their tests exclusively with NMN (which is what's fueling all the speculation about Sinclair's motives for doing so in most of the posts since the paper was posted).
You take my post the wrong way. I don't take anything away from Sinclair but he is the spin master. I didn't imply he was flawed or fraudulent. Look both sides of this ride on each others coat tales. He plays the press perhaps better than anyone in the field. So a tip of the hat to him.
Working in the media I can tell you he is one of the most polished interviewee's I've seen in awhile.
The Psoriasis angle is something I didn't know about SRT 2401, pretty neat. But we have to admit sirtuins are just one aspect of the equation. An important part by all indicators but raising NAD itself stimulates the sirtuins better than anything else.
Now I like competition but I really don't see any difference in what NMN and NR can do. At this point in time without any comparative data suggesting one is better than the other I see a draw or tie as to the effectiveness of either. NMN still needs to be broken down to NR to be absorbed at the cell membrane.
So from the sidelines where we sit I'm cheering both sides and like competition. A lot of whats going on at the moment however is who can attract the most grant money and who's NAD precursor molecule will dominate the globe. I think this is a win win for us as consumers.
I only included fraudulent since I have read that charge against Sinclair over the past decade but with no specifics given. Some have argued his early resveratrol experiment on mice was not replicable, and I have had a problem with him contradicting himself a few times over the years about resveratrol. But while annoyed at the time, I though those were pretty minor in the larger scheme of things.
Sinclair may well be using NMN to base a drug on to compete against a drug that might be made based on NR, but I'm not sure, and like you think this is win - win. That was mean to be my point to a couple of other posts - there could easily be an economic value to having competing drugs, and I think this is just the beginning as Sinclair told NPR Science Friday in 2013. He said then that "a lot of people are trying" to produce an anti-aging drug and didn't assume it was him who was in the lead.
Also tagged with one or more of these keywords: nicotinamide riboside, nicotinamide, nad boosting, charles brenner, david sinclair, leonard guarente, niagen, niacinamide, nicotinamide mononucleotide
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Also, despite the cost of supplementing with NR, the price seems to have moderated, and you can bet it's a heck of a lot cheaper than any prescription drug will be, if you can even get it. By the time his product gets approval, there is a definite prospect of further breakthroughs given the momentum that seems to be building in this field.
