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David Sinclair's biological age was 58 after taking 1000 mg of resveratrol

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#31 MikeDC

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Posted 03 March 2018 - 07:09 PM

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
He also said he started both metformin and NMN. Metformin will help a lot with diabetes. If he doesn’t take Resveratrol now, I don’t see why anyone would take it. Much better alternatives are available. At best Resveratrol is just an antioxidant.

Edited by MikeDC, 03 March 2018 - 07:10 PM.

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#32 hav

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Posted 03 March 2018 - 08:21 PM

 

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

 

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

 

 

Thanks for the missing detail.  I expected the blood-tests to be telomere length measurements but see they're biomarkers which his PowerPoint lists as Glucose, Vitamin D, Testosterone, hsCRP... he says there are 30-some in the InsideTracker test report...  and that Resveratrol's impact on them as a group is negligible compared to NMN.  Only issue I see is that the "biological age" thing is a calculated inference based on a correlation between those biomarkers and physical age.  Which might further skew things for a pre-diabetic.  Certainly suggests taking NMN might be a more practical way to manipulate all those markers than taking individual supplements.  Wonder if InsideTracker provides marker by marker "biological age" assumptions so one can decide if individual manipulation might be simpler, like if my only deficiency was Vitamin D, I'd just take that.

 

Howard


Edited by hav, 03 March 2018 - 08:44 PM.


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#33 bluemoon

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Posted 04 March 2018 - 04:21 PM

 

He also said he started both metformin and NMN. Metformin will help a lot with diabetes. If he doesn’t take Resveratrol now, I don’t see why anyone would take it. Much better alternatives are available. At best Resveratrol is just an antioxidant.

 

 

The last I read was in August 2015, Sinclair said he took 1,000 mg of resveratrol at breakfast along with a NAD+ precursor that turns out to be NMN. I assume the reason was the same as Elysium selling ptersotilbine with NR. 


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#34 Anthony_Loera

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Posted 05 March 2018 - 02:54 PM

 

 

He also said he started both metformin and NMN. Metformin will help a lot with diabetes. If he doesn’t take Resveratrol now, I don’t see why anyone would take it. Much better alternatives are available. At best Resveratrol is just an antioxidant.

 

 

The last I read was in August 2015, Sinclair said he took 1,000 mg of resveratrol at breakfast along with a NAD+ precursor that turns out to be NMN. I assume the reason was the same as Elysium selling ptersotilbine with NR. 

 

 

I still have not seen a study that shows Ptero activates Sirt1 (or any sirtuins)

I am not entirely sure why it would be in Elysium.

 

Anyone have a link to a study that shows Sirtuin activation of Ptero?

 

A


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#35 MikeDC

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Posted 05 March 2018 - 03:17 PM

He also said he started both metformin and NMN. Metformin will help a lot with diabetes. If he doesn’t take Resveratrol now, I don’t see why anyone would take it. Much better alternatives are available. At best Resveratrol is just an antioxidant.


The last I read was in August 2015, Sinclair said he took 1,000 mg of resveratrol at breakfast along with a NAD+ precursor that turns out to be NMN. I assume the reason was the same as Elysium selling ptersotilbine with NR.

I still have not seen a study that shows Ptero activates Sirt1 (or any sirtuins)
I am not entirely sure why it would be in Elysium.

Anyone have a link to a study that shows Sirtuin activation of Ptero?

A

If you search pterostilbene and Sirt1 on pubmed, you get 8 articles. Even though many studies show both Resveratrol and pterostilbene activate Sirt1. Clinical trials results show otherwise. Elysium made a big mistake using pterostilbene and their clinical trial results were negatively impacted by pterostilbene. The soon to be published Colorado NR trail will show much better health benefit than Elysium’s trial.
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#36 bluemoon

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Posted 05 March 2018 - 03:38 PM

 

 

The last I read was in August 2015, Sinclair said he took 1,000 mg of resveratrol at breakfast along with a NAD+ precursor that turns out to be NMN. I assume the reason was the same as Elysium selling ptersotilbine with NR. 

 

 

I still have not seen a study that shows Ptero activates Sirt1 (or any sirtuins)

I am not entirely sure why it would be in Elysium.

 

Anyone have a link to a study that shows Sirtuin activation of Ptero?

 

A

 

 

Since Pterostilbine is so close to resveratrol, I can see why Guarente would add it as a likely molecule to have a synergistic effect with NR as he stated when Eysium began to sell Basis.



#37 hav

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Posted 06 March 2018 - 09:43 PM

I still have not seen a study that shows Ptero activates Sirt1 (or any sirtuins)

I am not entirely sure why it would be in Elysium.

 

Anyone have a link to a study that shows Sirtuin activation of Ptero?

 

A

 

 

Don't think it does that either.  But it does achieve a number of similar effects via other pathways and has a higher bio-availability.  Good summary chart of studies/effects of resveratol, ptero, and a metabolite of ptero:

 

http://www.jfda-onli...0096-5/fulltext

 

Howard

 


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#38 Anthony_Loera

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Posted 06 March 2018 - 11:02 PM

 

I still have not seen a study that shows Ptero activates Sirt1 (or any sirtuins)

I am not entirely sure why it would be in Elysium.

 

Anyone have a link to a study that shows Sirtuin activation of Ptero?

 

A

 

 

Don't think it does that either.  But it does achieve a number of similar effects via other pathways and has a higher bio-availability.  Good summary chart of studies/effects of resveratol, ptero, and a metabolite of ptero:

 

http://www.jfda-onli...0096-5/fulltext

 

Howard

 

 

 

Thanks Hav,

 

I don't believe Pterostilbene has been shown to activate any sirtuins at this point.

 

Hmmm...Is it me or are most of the animal studies done with resveratrol in the article you link?

 

A


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#39 hav

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Posted 07 March 2018 - 08:07 PM

 

 

I still have not seen a study that shows Ptero activates Sirt1 (or any sirtuins)

I am not entirely sure why it would be in Elysium.

 

Anyone have a link to a study that shows Sirtuin activation of Ptero?

 

A

 

 

Don't think it does that either.  But it does achieve a number of similar effects via other pathways and has a higher bio-availability.  Good summary chart of studies/effects of resveratol, ptero, and a metabolite of ptero:

 

http://www.jfda-onli...0096-5/fulltext

 

Howard

 

 

 

Thanks Hav,

 

I don't believe Pterostilbene has been shown to activate any sirtuins at this point.

 

Hmmm...Is it me or are most of the animal studies done with resveratrol in the article you link?

 

A

 

 

Resverastrol is way more studied than ptero.  And the only one in that summary studied in humans... a diabetes study.  Which probably explains why Sinclair takes it.  Some folks on this forum who need to keep close monitor of their glucose levels have also reported this and observed greater effect mixing it with some of the more lipophilic resveratrol-related molecules. I seem to recall polydatin and luteolin being mentioned. I think ptero might do even better but that summary only goes up to Jan 2017... however, here's one from Aug 2017: https://www.ncbi.nlm...pubmed/28629731

 

Howard



#40 bluemoon

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Posted 08 March 2018 - 02:28 AM

 

 

Resverastrol is way more studied than ptero.  And the only one in that summary studied in humans... a diabetes study.  Which probably explains why Sinclair takes it.  Some folks on this forum who need to keep close monitor of their glucose levels have also reported this and observed greater effect mixing it with some of the more lipophilic resveratrol-related molecules. I seem to recall polydatin and luteolin being mentioned. I think ptero might do even better but that summary only goes up to Jan 2017... however, here's one from Aug 2017: https://www.ncbi.nlm...pubmed/28629731

 

Howard

 

 

So why do you think almost nobody cares about reveratrol anymore? Where are the human trials for reseveratrol? Evenn Sinclair called resveratrol the first generation health supplement in 2014 whereas he said: "We are now on the 5th generation with NR?" 


Edited by bluemoon, 08 March 2018 - 02:29 AM.

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#41 MikeDC

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Posted 08 March 2018 - 03:04 AM

Resverastrol is way more studied than ptero. And the only one in that summary studied in humans... a diabetes study. Which probably explains why Sinclair takes it. Some folks on this forum who need to keep close monitor of their glucose levels have also reported this and observed greater effect mixing it with some of the more lipophilic resveratrol-related molecules. I seem to recall polydatin and luteolin being mentioned. I think ptero might do even better but that summary only goes up to Jan 2017... however, here's one from Aug 2017: https://www.ncbi.nlm...pubmed/28629731

Howard
So why do you think almost nobody cares about reveratrol anymore? Where are the human trials for reseveratrol? Evenn Sinclair called resveratrol the first generation health supplement in 2014 whereas he said: "We are now on the 5th generation with NR?"
This is a review article that did a meta analysis on all Resveratrol clinical trials. The result is Resveratrol doesn’t change lipid profile. This means Resveratrol doesn’t activate Sirt1. Pterostilbene actually increases lipid profile. So pterostilbene is also not a sirt 1 activator. All the studies of Resveratrol on mice are trash. https://www.ncbi.nlm...clinical trials

Edited by MikeDC, 08 March 2018 - 03:05 AM.

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#42 hav

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Posted 09 March 2018 - 05:43 PM

This is a review article that did a meta analysis on all Resveratrol clinical trials. The result is Resveratrol doesn’t change lipid profile. This means Resveratrol doesn’t activate Sirt1. Pterostilbene actually increases lipid profile. So pterostilbene is also not a sirt 1 activator. All the studies of Resveratrol on mice are trash. https://www.ncbi.nlm...clinical trials

 

 

 

Sirt1 has a number of effects involving glucose and lipid metabolism but regulating the lipid profile isn't mentioned in this paper on Sirtuins in Glucose and Lipid Metabolism.  But they specifically mention sirt6 as having that effect.  So the study you cite and this paper taken together indeed suggest that resveratrol is not a sirt6 activator and would be the wrong supplement to take if improving your lipid profile were your only consideration.

 

Howard


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#43 MikeDC

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Posted 09 March 2018 - 06:01 PM

This is a review article that did a meta analysis on all Resveratrol clinical trials. The result is Resveratrol doesn’t change lipid profile. This means Resveratrol doesn’t activate Sirt1. Pterostilbene actually increases lipid profile. So pterostilbene is also not a sirt 1 activator. All the studies of Resveratrol on mice are trash. https://www.ncbi.nlm...clinical trials


Sirt1 has a number of effects involving glucose and lipid metabolism but regulating the lipid profile isn't mentioned in this paper on Sirtuins in Glucose and Lipid Metabolism. But they specifically mention sirt6 as having that effect. So the study you cite and this paper taken together indeed suggest that resveratrol is not a sirt6 activator and would be the wrong supplement to take if improving your lipid profile were your only consideration.

Howard

There are more evidence that Sirt1 regulate metabolic health than sirt6. Maybe both.
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#44 Castiel

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Posted 09 July 2018 - 09:50 PM

Resveratrol increased lifespan in fish, in yeast, in flies, in c. elegans, in mice with various disorders, in obese rodents, iirc.   In longer lived organisms, including normal mice, it seems hypothetically conceivable that NAD+ drops with age, and that limits resveratrol and stops it from being effective.

 

With a good source of NAD+ resveratrol's effectiveness should be restored even into advanced age, and has good but unproven potential.

 

I've heard that Fasting increases NAD+, so it too might aid, an alternate day fast protocol combined with resveratrol + nicotinamide riboside should help get very high NAD+, assuming it is true fasting increases NAD+ which seems reasonable.


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#45 MikeDC

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Posted 10 July 2018 - 02:16 AM

http://journals.plos...al.pone.0102406

300mg of Resveratrol had no effect on Sirt1 activity. But showed mito toxicity.
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#46 Castiel

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Posted 10 July 2018 - 02:32 AM

Would have to refind how was the prior study that said resveratrol didn't activate sirt1 rebutted.   I do seem to recall it had to do with something having to do with the assay mechanism invalidating the measuring by interfering with the results.

 

Additional research done later with proper assays revalidated resveratrol after the initial supposed counter finding of not activating sirt1, showing it did activate sirt1.

 

It also activates sirt6 at doses a 1000 times lower.

Resveratrol found to activate ancient stress response and at 1,000 times lower doses
Tracking the resveratrol-bound TyrRS in the nucleus, the researchers determined that it grabs and activates the protein PARP-1, a major stress response and DNA-repair factor thought to have a significant influence on lifespan. The scientists confirmed the interaction in mice injected with resveratrol. TyrRS’s activation of PARP-1 led, in turn, to the activation of a host of protective genes including the tumor-suppressor gene p53, and most interesting — the longevity genes FOXO3A and SIRT6.
The team’s experiments showed, however, that the TyrRS-PARP-1 pathway can be measurably activated by much lower doses of resveratrol — as much as 1,000 times lower — than were used in some of the more celebrated prior studies, including those focused on SIRT1. “Based on these results, it is conceivable that moderate consumption of a couple glasses of red wine (rich in resveratrol) would give a person enough resveratrol to evoke a protective effect via this pathway,” Sajish said. He also suspects that effects of resveratrol that only appear at unrealistically high doses may have confounded some prior findings.

http://www.kurzweila...health-benefits

 

Isn't FOXOA3 the centenarian gene? which in high activity can increase chances of reaching 100+?

 

EDIT

 

 

 

  A new study appears to offer vindication for an approach to anti-aging drugs that has been at the center of heated scientific debate in recent years. The new findings show for the first time that the metabolic benefits of the red wine ingredient known as resveratrol evaporate in mice that lack the famed longevity gene SIRT1.https://www.scienced...20501134209.htm

 

Think the following was the study.  Given the above showing in animal dependency on sirt1, there are ways for it to activate it within the cell that may elude some methods of measuring its enhancement of activity.

 

 

 

As we discussed in our February 10, 2010 blog article, researchers at Amgen found evidence that the apparent in vitro activation of SIRT1 by resveratrol depended on the substrate used in the assay. The Amgen group found that the fluorescent SIRT1 peptide substrate used in the Sirtris assay is a substrate for SIRT1, but in the absence of the covalently linked fluorophore, the peptide is not a SIRT1 substrate. Resveratrol did not activate SIRT1 in vitro as determined by assays using two other non-fluorescently-labeled substrates...
New evidence that STACs activate SIRT1 in vitro under certain conditions

 

On 8 March 2013, the journal Science published a report by Sirtris founder David A. Sinclair, Ph.D. (Harvard Medical School, Boston MA) and his colleagues [from academia and from Sirtris, GSK, and from Biomol (Plymouth Meeting, PA)] that identified conditions under which STACs activate SIRT1 in vitro. This research report was accompanied by a Perspective in the same issue of Science authored by Hua Yuan, Ph.D. and Ronen Marmorstein, Ph.D. (Wistar Institute, Philadelphia, PA)…

 

The researchers conclude that STACs act via a mechanism of direct “assisted allosteric activation” mediated by the Glu230-containing N-terminal activation domain of SIRT1. They further conclude that their findings support the hypothesis that allosteric activation of SIRT1 by STACs constitutes a viable therapeutic intervention strategy for many aging-related diseases. thus apparently vindicating the Sirtris/GSK development program.

https://biopharmcons...rtris-founders/

 


Edited by Castiel, 10 July 2018 - 02:50 AM.

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#47 renntenn

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Posted 11 September 2018 - 05:33 AM

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

 

 

My first ever forum post so I hope I am following protocol. 

 

@PAMPAGUY How do you know that the NR or NMN you are buying is real and not just some junk put in a pill? Thanks. 



#48 Phoebus

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Posted 17 September 2018 - 10:49 PM

http://journals.plos...al.pone.0102406

300mg of Resveratrol had no effect on Sirt1 activity. But showed mito toxicity.

 

from that study

 

 

 

Mitochondrial respiration in PmFBs was rapidly inhibited by RSV at 100–300 uM depending on the substrate examined. These results question the efficacy of a single dose of RSV at altering skeletal muscle and adipose tissue AMPK/SIRT1 activity in humans and suggest that RSV mechanisms of action in humans may be associated with altered cellular energetics resulting from impaired mitochondrial ATP production.

 

wow, that does not sound good at all. Does nothing positive and at least one negative thing


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#49 Oakman

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Posted 30 October 2018 - 07:03 PM

Sinclair bit all over the place on what he takes over time, so in reality, he's a bit like many of us. Even in his interviews, I've not heard any rationale for how much he takes, or even why he still take it, other than he says he's "more familiar" with resveratrol and so he and his father both take 1000 mg/day (along with other supps like NMN, etc.. One thing I would like to know is, 'is he taking resveratrol say, as a Japanese knotweed sourced product, which has a varying amount of trans-resveratrol plus cis-resveratrol or 100% trans-resveratrol'. As one would hope, as a scientist, he's being specific, but he hasn't said as far as I know.

 

It would make a big difference and something we to consider if trying to emulate his regime.


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#50 bluemoon

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Posted 30 October 2018 - 09:58 PM

Sinclair bit all over the place on what he takes over time, so in reality, he's a bit like many of us.  

 

I don't think Sinclair has been all over the place. In the past he was reluctant to say but in 2007 he said 320 mg of resveratol then around 2009 he said that he and his wife took 500 mg and up to 750mg. The last he has said about resveratrol was in 2015 when he told a Washington Post reporter that he sprinkled 1,000 mg of resveratol on his cereal each morning. 

 

With NMN, he has said 500 mg with his father, then 750 mg on a linked-in post, so he updates and added metformin. 



#51 Oakman

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Posted 31 October 2018 - 02:50 AM

I don't think Sinclair has been all over the place. In the past he was reluctant to say but in 2007 he said 320 mg of resveratol then around 2009 he said that he and his wife took 500 mg and up to 750mg. The last he has said about resveratrol was in 2015 when he told a Washington Post reporter that he sprinkled 1,000 mg of resveratol on his cereal each morning. 

 

With NMN, he has said 500 mg with his father, then 750 mg on a linked-in post, so he updates and added metformin. 

 

Ok gotcha... 320 mgs > 500 mgs > 750 mgs > 1000 mgs > 500 mgs > 750 mgs.... so not all over the place.  Oh, and you forgot here where he says 1000 mg, plus NMN, and metformin (at 1:05:25) this August. I'd be interested how he comes up with his dosing changes, perhaps we'll learn in his coming book?


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#52 bluemoon

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Posted 31 October 2018 - 05:45 AM

Ok gotcha... 320 mgs > 500 mgs > 750 mgs > 1000 mgs > 500 mgs > 750 mgs.... so not all over the place.  Oh, and you forgot here where he says 1000 mg, plus NMN, and metformin (at 1:05:25) this August. I'd be interested how he comes up with his dosing changes, perhaps we'll learn in his coming book?

 

Huh? It isn't "all over the place" if he simply increased his dosage of resveratol and NMN. Why are you putting resveratrol, NMN and metformin?  

 

I found Sinclair's linked in message from June: " I take 750 mg of NMN every morning, along with a gram of resveratrol and 500 mg of metformin."

 

At the talk you linked to he said "1 gram of  resveratol,  800 mg of metformin and his father takes 500 mg to 750 mg of NMN. 

 

These are very similar dosages. He said 1 gram of resveratol in 2015 so that hasn't changed at all. All that changed about NMN is that he increased to 750 mg from 500 mg. Sinclair said in 2014 that he thought you need 500 mg o 1000 mg of NMN or NR to notice a difference and that is what he is taking.

 

We have a good idea that more than 500 mg of NR doesn't raise NAD+ after 8 weeks so 1000mg is a waste if healthy. As I noted, Chromadex's commercial is not honest about this.



#53 Oakman

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Posted 31 October 2018 - 01:45 PM

^ Guess he's just self-experimenting like the rest of us. Good for him, hope he finds the best combo to use.



#54 PAMPAGUY

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Posted 31 October 2018 - 05:12 PM

Here is something to think about.  Dr. Peter Attia just had a podcast with Dr. Sinclair and he argues that NR and all NAD precussors raise the NAD levels, but the NAD never gets out of the liver into the mitochondria.  Feels it is a waste of money and time to take precussors.

  

https://www.scienced...01967?via=ihub=


Edited by PAMPAGUY, 31 October 2018 - 05:24 PM.

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#55 PAMPAGUY

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Posted 31 October 2018 - 05:51 PM

Sorry, it is located at 1:57

The only way to get it in the cell beyond the liver is intravenously.


Edited by PAMPAGUY, 31 October 2018 - 05:58 PM.


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#56 Rocket

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Posted 05 November 2018 - 11:37 PM

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

Well I guess that settles it. Sinclair said his 78 year old dad can climb a mountain, so it must be true. 


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