68 replies to this topic

[bluemoon]

I pointed this out on the NR thread...

 

Sinclair told The Washington Post that he was taking 1000 mg of resveratrol a day when he was 45 in 2015 and still had a biological age of 58 according to what he recently revealed in an interview.  Before he began taking 500 mg of NMN, he said his blood work showed that his biological age was that of a 58 year old but after the NMN, it had reversed to 32. 

 

This looks like the final nail in resveratrol's coffin.

 

the interview:

http://www.dailymail...ixir-youth.html

[Florian E.]

Mechanisms of Mild Cellular Stress Response

http://www.diss.fu-b...is_000000103466

 

Maybe Dr. Sinclair has overdone it with the "mild stress" ROS production 

 

But i think nicotinamide riboside is enough for sirt1 activation (without mild stress).

And also fisetin could be a better sirt1 activator.

[maxwatt]

The daily mail is sort of like the National Inquirer.  Still there might sometimes be a grain of truth in some of their articles.  Whatever virtues NMN may have in regards to resveratrol, I have my doubts about this article.

 

I believe the blood test mentioned in the daily mail was this one reported in Nature.  https://www.nature.c...icles/srep17282

Quoting from the paper: "We found smoking, high BMI and consumption of sugar-sweetened beverages to increase the predicted chronological age by 2–6 years, while consumption of fatty fish, drinking moderate amounts of coffee and exercising reduced the predicted age by approximately the same amount."

 

So it looks like the test can give a result +/- 2 to 6 years from ones chronological age.  The Mail gave a range for Sinclair of +/-13 years.   I do note that Sinclair's measures are self-reported, perhaps inaccurately.

 

The Daily Mail article quotes Sinclair as mentioning two substances - both drugs - that may fight aging:  metformin and rapamycin.  Both of which are discussed extensively elsewhere in Longecity's forums.

 

 

 

Edited by maxwatt, 28 April 2017 - 08:11 PM.

[PAMPAGUY]

How much NR to equal the 500 mg NAD Sinclair was taking daily?  Sinclair is paying appx $1000 month for the NAD.

 

Anyone know.

 

Thanks

[bluemoon]

The daily mail is sort of like the National Inquirer.  Still there might sometimes be a grain of truth in some of their articles.  Whatever virtues NMN may have in regards to resveratrol, I have my doubts about this article.

 

I believe the blood test mentioned in the daily mail was this one reported in Nature.  https://www.nature.c...icles/srep17282

Quoting from the paper: "We found smoking, high BMI and consumption of sugar-sweetened beverages to increase the predicted chronological age by 2–6 years, while consumption of fatty fish, drinking moderate amounts of coffee and exercising reduced the predicted age by approximately the same amount."

 

So it looks like the test can give a result +/- 2 to 6 years from ones chronological age.  The Mail gave a range for Sinclair of +/-13 years.   I do note that Sinclair's measures are self-reported, perhaps inaccurately.

 

The Daily Mail article quotes Sinclair as mentioning two substances - both drugs - that may fight aging:  metformin and rapamycin.  Both of which are discussed extensively elsewhere in Longecity's forums.

 

 

There is much more than just a "grain of truth" in that Daily Mail article, which includes several quotes and explanations by Sinclair. We don't know which aging test Sinclair used but "soulprogrammer" posted on the NR Curated thread that it may have been the free site Aging AI 2.0 where one inputs 30 to 40 blood test results to get a "biological age."

 

After taking NR for quite a while (dose not mentioned), a 62 year old entered his data and got 28 years while a 59 year old got 39 years - but pre NR results not used. The test claims an error of +/- 5 years, and that can depend on how much data you enter.

 

Maxwatt, I don't see any mention in the Daily Mail article of +/- 13 years for Sinclair's age as you wrote. Sinclair, 47, said his pre NMN biological age was estimated to be 58 and after taking NMN for 3 months had an estimate of 32 years old.  Is Sinclair lying about his estimated biological age as you suggest? It is possible, but I doubt it.

 

@PAMPAGUY: Notice Sinclair never mentions NR but last I read was taking 1000 mg of resveratrol a day. I don't think anyone knows what effects 500 mg of NR would give compared to 500 mg of NMN.

[bluemoon]

I forgot to add that it is possible Sinclair stopped taking his 1000 mg of resveratrol and any other supplements for a while in order to get an NMN only "before" reading. If so, he should have said that in the interview. 

[PAMPAGUY]

BLUEMOON - I purchase 250 mg NR for $130.00 for 180 capsules.  Even taking 2 capsules a day that is so much cheaper than $1000 month.  I believe Sinclair said he is going to do clinical trials on NMN.  Can't make very much money on NR, so expect to see a drug similar to the rapalogs for rapamycin where you need a RX and they can charge plenty.

 

Take a look a study 1 at this site and see if you can make sense of the chart of increase in NMN by different dosages of NR.

 

 http://alivebynature.com/about-niagen/

 

another david sinclair video a month ago about NMN

 

 

 

 

Edited by PAMPAGUY, 29 April 2017 - 09:23 PM.

[bluemoon]

BLUEMOON - I purchase 250 mg NR for $130.00 for 180 capsules.  Even taking 2 capsules a day that is so much cheaper than $1000 month.  I believe Sinclair said he is going to do clinical trials on NMN.  Can't make very much money on NR, so expect to see a drug similar to the rapalogs for rapamycin where you need a RX and they can charge plenty.

 

Take a look a study 1 at this site and see if you can make sense of the chart of increase in NMN by different dosages of NR.

 

 http://alivebynature.com/about-niagen/

 

another david sinclair video a month ago about NMN

 

 

 

Thanks for linking the video. My understanding is that NMN first converts to NR and Sinclair doesn't mention that. Maybe my impression was wrong. Yet if NR proves to be helpful based on the results of the 140 person Chromadex study coming out in a few weeks, why would people take NMN that costs maybe twice as much by the time it goes to market in 2020 to 2023? 

 

NR researcher Charles Brenner has said resveartrol is worthless and is skeptical that pterostilbine does much, but I doubt he is right about either.

Edited by bluemoon, 29 April 2017 - 09:35 PM.

[PAMPAGUY]

NR is a precursor to NAD which converts to NMN.  That is the mechanism as I understand it.

 

NMN + NR trial in Japan    https://www.nature.c...es/npjamd201621

 

Also, Basis has NR and pterostilbene.  They believe the two together are synergistic.  So it would be interesting if Sinclair continued on his Resveratrol when he started the NMN.  I'm not aware of anyone who has got the results that his father got from taking the NMN. (76 yo feeling like a 20-30 yo.)

[bluemoon]

 

  So it would be interesting if Sinclair continued on his Resveratrol when he started the NMN.  

 

We don't know but Sinclair saw the results of his NMN mouse trial in 2013 and told the Washington Post in August 2015 that he was taking 1000 mg of resveratrol a day. 

 

His recent quote doesn't say one way or another if he stopped the resveratrol for a while to take the "before NMN" test. Sinclair has a way of being unclear and leaving out details about things like this. 

[PeaceAndProsperity]

I am wondering from a purely scientific perspective, is it possible that David Sinclair told a lie to bolster his financial gains?

[maxwatt]

 

....

 

Maxwatt, I don't see any mention in the Daily Mail article of +/- 13 years for Sinclair's age as you wrote. Sinclair, 47, said his pre NMN biological age was estimated to be 58 and after taking NMN for 3 months had an estimate of 32 years old.  Is Sinclair lying about his estimated biological age as you suggest? It is possible, but I doubt it.

 

 

You quoted the daily mail as: with resveratrol at age "45 in 2015 and [he] still had a biological age of 58 according to what he recently revealed in an interview.  Before he began taking 500 mg of NMN, he said his blood work showed that his biological age was that of a 58 year old but after the NMN, it had reversed to 32. 

"

I subtracted 45 from 58 to get 13, and 32 from 45 to get 13.  Hence +/- 13.

 

I know one of Sinclair's former postdoc students.  He might ask for us what Sinclair was using for a test.

 

In the meantime Rapamycin looks more promising, but I am not ruling out NMN or dasatinib and quercetin, or a host of other molecules as being potentially beneficial. We need more data.

 

FWIW, for what its worth, I took one of those "age tests" and scored 14 years younger than my birth year.  I'd been taking resveratrol for years.  Tried NR with no noticeable effect.  And this proves nothing. 

Edited by maxwatt, 01 May 2017 - 03:28 AM.

[soulprogrammer]

 

 

....

 

Maxwatt, I don't see any mention in the Daily Mail article of +/- 13 years for Sinclair's age as you wrote. Sinclair, 47, said his pre NMN biological age was estimated to be 58 and after taking NMN for 3 months had an estimate of 32 years old.  Is Sinclair lying about his estimated biological age as you suggest? It is possible, but I doubt it.

 

 

You quoted the daily mail as: with resveratrol at age "45 in 2015 and [he] still had a biological age of 58 according to what he recently revealed in an interview.  Before he began taking 500 mg of NMN, he said his blood work showed that his biological age was that of a 58 year old but after the NMN, it had reversed to 32. 

"

I subtracted 45 from 58 to get 13, and 32 from 45 to get 13.  Hence +/- 13.

 

I know one of Sinclair's former postdoc students.  He might ask for us what Sinclair was using for a test.

 

In the meantime Rapamycin looks more promising, but I am not ruling out NMN or dasatinib and quercetin, or a host of other molecules as being potentially beneficial. We need more data.

 

FWIW, for what its worth, I took one of those "age tests" and scored 14 years younger than my birth year.  I'd been taking resveratrol for years.  Tried NR with no noticeable effect.  And this proves nothing. 

 

 

 

which "age tests" you took? Can you give the link?

[maxwatt]

Try http://www.aging.ai/

[Mind]

I apologize for hijackng this thread for a bit. Since people are talking about aging tests, here is a very cheap test for DNA methylation (which is considered a bio-marker of aging): http://www.longecity...ation-analysis/ LongeCity members get a 30% discount, but even without the discount, the cost is cheap. Just wanted to see if anyone else has had this measured. It would be neat to see comparisons between the LongeCity crowd.

[bluemoon]

 

 

I subtracted 45 from 58 to get 13, and 32 from 45 to get 13.  Hence +/- 13.

 

I know one of Sinclair's former postdoc students.  He might ask for us what Sinclair was using for a test.

 

In the meantime Rapamycin looks more promising, but I am not ruling out NMN or dasatinib and quercetin, or a host of other molecules as being potentially beneficial. We need more data.

 

FWIW, for what its worth, I took one of those "age tests" and scored 14 years younger than my birth year.  I'd been taking resveratrol for years.  Tried NR with no noticeable effect.  And this proves nothing. 

 

 

Oh, OK. This sentence confused me: "So it looks like the test can give a result +/- 2 to 6 years from ones chronological age.  The Mail gave a range for Sinclair of +/-13 years." since the first is an error bar.

 

By the way, did you know that my Uncle Bill just put out an email that Longevinex is announcing a breakthrough study on the effects of resveratrol on the eye early this month? He strongly recommends that we stock up on Longevinex now since he expects it to soon sell out. Don't delay!   

 

 

[Forever21]

Is my Nad+ good enough?

http://www.lifeexten...ell-Regenerator

 

What should I buy to join in the game?

[maxwatt]

....

 

By the way, did you know that my Uncle Bill just put out an email that Longevinex is announcing a breakthrough study on the effects of resveratrol on the eye early this month? He strongly recommends that we stock up on Longevinex now since he expects it to soon sell out. Don't delay!   

 

 

 

 

Ha Ha.

 

Eye am still waiting to see the study.

 

I would recommend also taking pterostilbene (30 mg) or resveratrol (300mg) if you are taking NR.  and NAD doesn't work, doesn't get into the blood.
 

[Rosanna]

 

....

 

By the way, did you know that my Uncle Bill just put out an email that Longevinex is announcing a breakthrough study on the effects of resveratrol on the eye early this month? He strongly recommends that we stock up on Longevinex now since he expects it to soon sell out. Don't delay!   

 

 

 

 

Ha Ha.

 

Eye am still waiting to see the study.

 

I would recommend also taking pterostilbene (30 mg) or resveratrol (300mg) if you are taking NR.  and NAD doesn't work, doesn't get into the blood.
 

 

 

Sorry to jump in, I'm new here so not clear on forum etiquette yet....can I ask, is it worth (safe?) taking BOTH pterostilbene and resveratrol with NR?

 

Also, wondering if the japanese knotweed version is considered safe in general?  (sorry if a very basic question, I've considered longevinex, but I have two bottles from my local store of 100mg resveratrol / japanese knotweed atm)  Thanks.

[bluemoon]

 

Sorry to jump in, I'm new here so not clear on forum etiquette yet....can I ask, is it worth (safe?) taking BOTH pterostilbene and resveratrol with NR?

 

Also, wondering if the japanese knotweed version is considered safe in general?  (sorry if a very basic question, I've considered longevinex, but I have two bottles from my local store of 100mg resveratrol / japanese knotweed atm)  Thanks.

 

Elysium's cofounder Leonard Guarente said in 2015 that he was taking BASIS which is NR and 50 mg of pterostilbine along with 250 mg of resveratrol but the last two are sumilar so I don't know why. At any rate, he thought it was safe and no reason to think it wouldn't be. David Sinclair said in 2015 that he was taking 1000 mg of resveratrol a day but who knows if he is still taking that with NMN.  

[maxwatt]

I believe it is safe to take both pterostilbene and resveratrol together, though it may be unnecessary as the effects overlap aonciderably, thogh pterostilbene is stronger (less required) but more expensive.

The knotweed extract is safe, as the extraction and purification technology have improved so as to reduce the amount of impuruties sch as emodin.

 

[MikeDC]

https://academic.oup...edFrom=fulltext

Both Resveratrol and pterostilbene raises cholesterol at high doses. They will not extend lifespan for sure.

[MikeDC]

I am wondering from a purely scientific perspective, is it possible that David Sinclair told a lie to bolster his financial gains?

Sinclair is a scam artist. Resveratrol does nothing at low doses. At high doses it is harmful and raises LDL. A NMN mice study showed 300mg/kg only raised NAD+ by 14% in the liver and muscle while another paper showed 185mg/kg NR raised NAD+ by 100%. NR is about 64 fold more effective than NMN at raising NAD+.

[tunt01]

Sinclair's viewpoint is the same as Guarente, in that one needs NAD+ coupled with a SIRT1 activator to make any meaningful impact and invoke 'pro-longevity' transcription factors.  Tossing out a resveratrol only trial and suggesting Sinclair is a scam artist, is pretty disingenuous and petty.

 

 

[MikeDC]

Sinclair's viewpoint is the same as Guarente, in that one needs NAD+ coupled with a SIRT1 activator to make any meaningful impact and invoke 'pro-longevity' transcription factors. Tossing out a resveratrol only trial and suggesting Sinclair is a scam artist, is pretty disingenuous and petty.

They are both wrong. NAD+ is the real activator. Resveratrol and pterostilbene don’t activate Sirt1. Elysium basis trial revealed the bad effects of pterostilbene. NR in its own is very effective at lowering cholesterol. But that effect is negated by pterostilbene. If Resveratrol and pterostilbene can’t improve metabolism and actually make it worse, then they are not Sirt1 activators. So far only NR and NMN are effective Sirtuin activators. NAM and Niacin can increase NAD+, but the positive effect from higher NAD+ is countered by their inhibitory effect on Sirt1. http://www.timelessl...atio-influence/

Edited by MikeDC, 26 February 2018 - 07:57 PM.

[maxwatt]

 

Sinclair's viewpoint is the same as Guarente, in that one needs NAD+ coupled with a SIRT1 activator to make any meaningful impact and invoke 'pro-longevity' transcription factors. Tossing out a resveratrol only trial and suggesting Sinclair is a scam artist, is pretty disingenuous and petty.

They are both wrong. NAD+ is the real activator. Resveratrol and pterostilbene don’t activate Sirt1. Elysium basis trial revealed the bad effects of pterostilbene. NR in its own is very effective at lowering cholesterol. But that effect is negated by pterostilbene. If Resveratrol and pterostilbene can’t improve metabolism and actually make it worse, then they are not Sirt1 activators. So far only NR and NMN are effective Sirtuin activators. NAM and Niacin can increase NAD+, but the positive effect from higher NAD+ is countered by their inhibitory effect on Sirt1. http://www.timelessl...atio-influence/

 

 

Mike- there have been complaints that you are shilling NR inappropriately, in the more-or-less moribund resveratrol forum.  You have been warned not to do this in the past.  Never the less, you have provided an interesting link to a discussion of a study   that is indexed in pubmed.  However the conclusion of the study does not seem to support your assertion, though as far as I can see it doesn't negate it either:  (A reference to studies showing NR alone can lower cholesterol would be helpful but it more properly belongs in an NR forum.)

 

"All tested sirtuin deacylase activities showed sensitivity to NADH in this assay. However, the inhibitory concentrations of NADH in these assays are far greater than the predicted concentrations of NADH in cells; therefore, our data indicate that NADH is unlikely to inhibit sirtuins in vivo These data suggest a re-evaluation of the sirtuins as direct sensors of the NAD(+)/NADH ratio."

 

Many other studies seem to suggest resveratrol (and pterostilbend?) do not act via sirtuin binding.  I suspect many of resveratrol's effects are due to PPAR-gamma activity.  But that's another topic.

[MikeDC]

 

 

Sinclair's viewpoint is the same as Guarente, in that one needs NAD+ coupled with a SIRT1 activator to make any meaningful impact and invoke 'pro-longevity' transcription factors. Tossing out a resveratrol only trial and suggesting Sinclair is a scam artist, is pretty disingenuous and petty.

They are both wrong. NAD+ is the real activator. Resveratrol and pterostilbene don’t activate Sirt1. Elysium basis trial revealed the bad effects of pterostilbene. NR in its own is very effective at lowering cholesterol. But that effect is negated by pterostilbene. If Resveratrol and pterostilbene can’t improve metabolism and actually make it worse, then they are not Sirt1 activators. So far only NR and NMN are effective Sirtuin activators. NAM and Niacin can increase NAD+, but the positive effect from higher NAD+ is countered by their inhibitory effect on Sirt1. http://www.timelessl...atio-influence/

 

 

Mike- there have been complaints that you are shilling NR inappropriately, in the more-or-less moribund resveratrol forum.  You have been warned not to do this in the past.  Never the less, you have provided an interesting link to a discussion of a study   that is indexed in pubmed.  However the conclusion of the study does not seem to support your assertion, though as far as I can see it doesn't negate it either:  (A reference to studies showing NR alone can lower cholesterol would be helpful but it more properly belongs in an NR forum.)

 

"All tested sirtuin deacylase activities showed sensitivity to NADH in this assay. However, the inhibitory concentrations of NADH in these assays are far greater than the predicted concentrations of NADH in cells; therefore, our data indicate that NADH is unlikely to inhibit sirtuins in vivo These data suggest a re-evaluation of the sirtuins as direct sensors of the NAD(+)/NADH ratio."

 

Many other studies seem to suggest resveratrol (and pterostilbend?) do not act via sirtuin binding.  I suspect many of resveratrol's effects are due to PPAR-gamma activity.  But that's another topic.

 

I am sorry if my post was interpreted as pumping NR. But Resveratrol and Pterostilbene are not SIrt1 activators. I remember reading a paper that showed Resveratrol causes stress in cells. Any good effects are due to stress response. When both Resveratrol and Pterostillbene are shown to increase cholesterol in high doses, you have to question the theory that it can activate sirt1 and improve metabolic health.  The amount of research dollars and money wasted on resveratrol supplement is huge.

[hav]

Unfortunately thanks to a sleazy interview/article its not clear exactly when Sinclair took his blood-test that yielded the biological age of 58.  Only says before he took NMN. Which might also be before he took 1000 mg/day of resveratrol in 2015.  Would expect a competent scientist to document before and after different treatments and a competent reporter to know enough to ask.

Btw, curious that he mixes resveratrol with yogurt. Wonder if he takes NMN that way too.

 

Howard

[MikeDC]

Unfortunately thanks to a sleazy interview/article its not clear exactly when Sinclair took his blood-test that yielded the biological age of 58. Only says before he took NMN. Which might also be before he took 1000 mg/day of resveratrol in 2015. Would expect a competent scientist to document before and after different treatments and a competent reporter to know enough to ask.

Btw, curious that he mixes resveratrol with yogurt. Wonder if he takes NMN that way too.

Howard

Resveratrol was discovered long time ago. He probably has been taking it for over 10 years.

[bluemoon]

Unfortunately thanks to a sleazy interview/article its not clear exactly when Sinclair took his blood-test that yielded the biological age of 58.  Only says before he took NMN. Which might also be before he took 1000 mg/day of resveratrol in 2015.  Would expect a competent scientist to document before and after different treatments and a competent reporter to know enough to ask.

Btw, curious that he mixes resveratrol with yogurt. Wonder if he takes NMN that way too.

 

Howard

 

My impression is that Sinclair stopped using resveratrol and saw his age increase to 58 and then started NMN but here is what he said in the presentation linked below starting at 34:25: 

 

1) He has been measuring his blood for 6 years and the talk was given in 2016 or 2017 so from 2010 to 2011 using that system yet he has also said he measured blood the first 6 months taking resveratrol around 2002.  

 

2) Sincair then said he saw his age go up until it reached 57 in 2014, then started taking metformin since he was pre-diabetic and NMN. After a peak of 58, within three months his age quickly fell to 32 years old. (from 35:00)

 

3) Sinclair said he felt and looked younger - "certainly I had more energy." 

 

4) He concludes that part saying his 78 year old father took NMN as well and could climb a   mountain as if in his 30s whereas Sinclair's brother, who isn't taking NMN, cold barely keep up.

 

34:25 on measuring aging and taking NMN:

 

https://www.youtube....h?v=hgQM9l8RWCw