2255 replies to this topic

[stefan_001]

 

I think the study shows 3 things:

1) NAD+ boosting recovers muscle

 

2) NR performs better than nicotinamide

3) The dosing might not need to be high as its not needed to recover NAD+. My own speculation is that the body start off with having an abundance of NAD+ and problems start when a certain threshold low value is achieved. So we may only need to boost till this threshold.

 

NR performs better than nicotinamide only in mNKO mice. Means they turned off Nampt : muscle-specific Nampt knockouts

 

They explain the small increase is due to the fact most NR is actually converted into Nicotinamide before it reach the muscle (targeted area).

 

Disproportion does not mean bad at all. They dont see negative result there. At least I dont see where after reading their graph

 

Actually what I see is: NR increase just a bit NAD+ when Nampt is turned off, the result looks clear to me. NR fail to recover mNKO mice from their state.

 

So Bryan and Stefan, you understood this not correctly: "NAD can disproportionately modulate aerobic metabolism". Why ? Because this just means that mitochondria isolated from C2C12 myotubes treated with FK866 and NR, you have NR that does not act proportionately in its ability to increase back complex I-dependent respiratory O2 consumption and NAD amount in mito. It seems at 10uM NR you reach the point where the respiratory is optimal and will remain stable while you increase more NAD with better dose. Thats all !

 

I dont mean the crash is not possible, but this study does not show us that. Its more a report for me of how important is Nampt once again, so this is my targeted area recently...

 

It also show NR in low dose can have positive effect

 

Hi Tom, I would describe it differently: this study shows that "NR, at least, performs better than nicotinamide in mNKO mice".  I thought the difference was actually quite impressive, more than I expected. Check figure S5, I attached a cutout from it.

 

This is the clarification the authors gave with regards to NAD concentration:

"we were surprised to find that NR exerts only a subtle influence on the steady-state concentration of NAD in muscles. Our tracer studies suggest that this is largely attributable to breakdown of orally delivered NR into NAM prior to reaching the muscle. Nonetheless, our results indicate that NR is more effective than NAM for reversing mNKO phenotypes (Figure S5). The correlation between the NAD content and the respiratory capacity of isolated mitochondria, even in cultured myotubes (Figure 4), supports the model that subtle changes in NAD can disproportionately modulate aerobic metabolism. It is important to note that NAD turnover may vary independently from NAD concentration and that small changes in average tissue concentration might reflect larger changes in specific cells or subcellular compartments. It is also possible that intramuscular conversion of NAD into secondary messengers potently influences calcium homeostasis, which is both essential to muscle contraction and can independently modulate mitochondrial respiration"

 

So while your statement is true it appears to not matter from an impact perspective.

Attached Files

•  namvsnr.JPG   56.05KB   1 downloads

[Tom Andre F. (ex shinobi)]

Yes Stefan I agree :" NR, at least, performs better than nicotinamide in mNKO mice" this is what I mean.

 

and yes clearly small increase in NAD is what they show give strong benefit at the mito level. My main point is that this study does not show concern about high dose NR bringing too much NAD since there is actually not really too much. Once the pool is high the effect does not increase above what is healthy state. So our only concern for now should be our declining NAD while we age.

Edited by Tom Andre F. (ex shinobi), 12 August 2016 - 08:37 PM.

[Tom Andre F. (ex shinobi)]

 

 

3.  There is some discussion of Metformin's role in beta amyloid generation is via activation of AMPK that leads to upregulation of BACE1 (one of the biggest problem in ALZ pathology).   SOURCE

 

I've seen literature and the sourced article suggesting to combine insulin + metformin to treat ALZ.  I'm not sure exactly of the pathway that is restored by insulin, such that BACE1 is inhibited.  I suspect it's something like PI3K/Akt, that a poor man's solution might be to take Lipoic Acid, which is a potential insulin mimetic.

 

 

Hi Prophets,

 

actually if metformin has any bad value for ALZ its not due to AMPK :

 

a previous study gave some speculation:

 

Roles of AMP-activated protein kinase in Alzheimer's disease.

Abstract

AMP-activated protein kinase (AMPK), a master regulator of cellular energy homeostasis and a central player in glucose and lipid metabolism, is potentially implicated in the pathogenesis of Alzheimer's disease (AD). AMPK activity decreases in AD brain, indicating decreased mitochondrial biogenesis and function. Emerging evidence demonstrates that AMPK activation is a potential target for improving perturbed brain energy metabolism that is involved in the pathogenesis of AD. The roles of AMPK in the pathogenesis of AD include β-amyloid protein (Aβ) generation and tau phosphorylation. In particular, AMPK may regulate Aβ generation through modulating neuronal cholesterol and sphingomyelin levels and through regulating APP distribution in the lipid rafts. AMPK is activated by phosphorylation of Thr-172 by LKB1 complex in response to increase in the AMP/ATP ratio and by calmodulin-dependent protein kinase kinase-beta in response to elevated Ca(2+) levels, which contributes to regulating Aβ generation. AMPK is a physiological tau kinase and can increase the phosphorylation of tau at Ser-262. AMPK can also directly phosphorylate tau at Thr-231 and Ser-396/404. Furthermore, AMPK activation decreases mTOR signaling activity to facilitate autophagy and promotes lysosomal degradation of Aβ. However, AMPK activation has non-neuroprotective property and may lead to detrimental outcomes, including Aβ generation and tau phosphorylation. Therefore, it is still unclear whether AMPK could serve a potential therapeutic target for AD, and hence, further studies will be needed to clarify the role of AMPK in AD.

 

this is from 2012.. Then in 2015, they came back with:

 

AMPK activation ameliorates Alzheimer's disease-like pathology and spatial memory impairment in a streptozotocin-induced Alzheimer's disease model in rats.

 

Abstract

Collecting evidence has shown that type 2 diabetes mellitus is a high risk factor of late-onset Alzheimer's disease (AD); the energy metabolic dysfunction is thought to be a convergent point of the two diseases. However, the underlying mechanisms of diabetes-associated AD are still unclear. In the current study, we investigated the roles of AMPK in diabetes-related AD-like pathologic features in models of intracerebroventricular-streptozotocin (ICV-STZ) animals. Rats infused with STZ (3 mg/kg, once) were followed by injection of AICAR (AMPK activator) or vehicle via ICV. We found that the level of p-AMPK (active type of AMPK) and SIRT1 activity were decreased and the level of phosphorylated tau was increased at Ser396 and Thr231 sites in ICV-STZ rats when compared with control rats. Mitochondria from ICV-STZ rats displayed a significant decrease in mitochondrial membrane potential, complex I activity, ATP level, and superoxide dismutase activity as well as an increase of reactive oxygen species production when compared with that from control rats. Meanwhile the number of apoptotic cell confirmed by cleaved caspase-3 (active type of caspase-3) staining was also stronger in ICV-STZ rats than control rats. All pathological changes including biochemistry and cognitive function could be mitigated through rescuing AMPK activity with its specific activator (AICAR) in ICV-STZ rats. Taken together, these results suggested that AMPK activation improves AD-like pathological changes via repairing mitochondrial functions in ICV-STZ rats.

 

[tunt01]

 

Kapetanovic, I., Muzzio, M., Huang, Z., Thompson, T., & McCormick, D. (2010). Pharmacokinetics, oral bioavailability, and metabolic profile of resveratrol and its dimethylether analog, pterostilbene, in rats. Cancer Chemotherapy And Pharmacology, 68(3), 593-601. doi:10.1007/s00280-010-1525-4

 

 

Everything I've seen says it's in the blood longer due to the methyl group.  AFAIK, it's the same thing as resveratrol plus a methyl group.  If Resveratrol activates SIRT1, then pterostilbene probably should be doing the same

[stefan_001]

Yes Stefan I agree :" NR, at least, performs better than nicotinamide in mNKO mice" this is what I mean.

 

and yes clearly small increase in NAD is what they show give strong benefit at the mito level. My main point is that this study does not show concern about high dose NR bringing too much NAD since there is actually not really too much. Once the pool is high the effect does not increase above what is healthy state. So our only concern for now should be our declining NAD while we age.

 

Agree with that!! i knew we could do it :-)

[Daniscience]

Thanks prophets. Resveratrol is known to activate SIRT1. My question though was about the far more bioavailable pterostilbene that stays in the system a lot longer (and is less expensive). People keep claiming it activates SIRT1 and Elysium puts it in their Basis Nicotinamide Riboside for that very reason yet there is little evidence that it does and there's contradictory evidence at that.

 

 

 

Kapetanovic, I., Muzzio, M., Huang, Z., Thompson, T., & McCormick, D. (2010). Pharmacokinetics, oral bioavailability, and metabolic profile of resveratrol and its dimethylether analog, pterostilbene, in rats. Cancer Chemotherapy And Pharmacology, 68(3), 593-601. doi:10.1007/s00280-010-1525-4

 

 

Everything I've seen says it's in the blood longer due to the methyl group.  AFAIK, it's the same thing as resveratrol plus a methyl group.  If Resveratrol activates SIRT1, then pterostilbene probably should be doing the same

 

Good point.

 

So, in your opinion, would this be a good all-round choice?

https://www.thorne.c...t/dp/resveracel

 

It includes NR, Trans-Resveratrol, quercetin, and betaine as a methylator. I am a total noob at NR and resveratrol and if that thing is garbage please warn me before purchasing lol. My main wish is to reverse metabolic syndrome, (aka fat loss, energy boost, and hunger control)

[tunt01]

Hi Prophets,

 

actually if metformin has any bad value for ALZ its not due to AMPK :

 

 

I think you are correct, because AICAR in similar models does not seem to induce amyloid beta generation like Metformin.  It's not clear to me what is causing the Abeta generation.  It must be some combination of AMPK + other effects of metformin, such that inhibiting AMPK eliminates this combination.

[tunt01]

 

 

 

 

So, in your opinion, would this be a good all-round choice?

https://www.thorne.c...t/dp/resveracel

 

It includes NR, Trans-Resveratrol, quercetin, and betaine as a methylator. I am a total noob at NR and resveratrol and if that thing is garbage please warn me before purchasing lol. My main wish is to reverse metabolic syndrome, (aka fat loss, energy boost, and hunger control)

 

 

 

 

That's a really neat supplement.  I was looking for something like that.  I've been taking pterostilbene (50 mg) + NR (100 mg) + betaine (500 mg).

 

I was thinking I would like to have a pill with maybe 5-10 mg reseveratrol, 50 mg pterostilbene, 50-100 mg quercetin.  Then I would add the betaine myself.  This is a nifty supplement.

[tunt01]

I think maybe SIRT1 is indirectly activated by Resveratrol via AMPK.  

 

It seems like Resveratrol alters Ca2+ causing CAMKKB to activate AMPK.  AMPK then upregulates SIRT1.  AMPK and SIRT1 really go hand in hand with energy sensing and cellular response.

 

 

 

 

 

 

 

Ruderman, N., Julia Xu, X., Nelson, L., Cacicedo, J., Saha, A., Lan, F., & Ido, Y. (2010). AMPK and SIRT1: a long-standing partnership?. AJP: Endocrinology And Metabolism, 298(4), E751-E760. doi:10.1152/ajpendo.00745.2009

 

 

 

We really should have a group buy for AICAR.

 

EDIT:

 

 

Here is a better pathway description of Resveratrol specifically that compliments the above diagram from Mouchiroud, Auwerx 2013.  

 

Resveratrol indirectly activating SIRT1 in an AMPK-dependent manner.

 

 

 

Mouchiroud, L., Houtkooper, R., & Auwerx, J. (2013). NAD + metabolism: A therapeutic target for age-related metabolic disease . Critical Reviews In Biochemistry And Molecular Biology,48(4), 397-408. doi:10.3109/10409238.2013.789479

 

Edited by prophets, 13 August 2016 - 02:54 PM.

[Nate-2004]

Though totally off topic from NR, this is the first I'm hearing of AICAR. Doesn't seem available to the general public at the moment.

 

Thanks for the info on pterostilbene. I had posted a thread about this study a while back and I'm still not entirely convinced pterostilbene is activating SIRT1 even if it is just resveratrol with a methyl group. 

 

Speaking of SIRT1:

 

They explain the small increase is due to the fact most NR is actually converted into Nicotinamide before it reach the muscle (targeted area).

 

Without rummaging through this entire thread hasn't it been shown that taking nicotinamide riboside does not in fact inhibit SIRT1 and that it activates it? If so, doesn't that tell us something about its dropping the ribose before entering muscular tissue? If nicotinamide on its own inhibits SIRT1 and NR activates it, then this is either not true or something is amiss here.  Because if it were converted to NAM before reaching the targeted area, then wouldn't it inhibit SIRT1?

Edited by Nate-2004, 13 August 2016 - 02:48 PM.

[Tom Andre F. (ex shinobi)]

Nate, it was explained that we shouldnt be concern about it in vivo since both actually increase NAD and means turns on the sirtuins. So as far as you increase your NAD level, you safe with sirtuin inhibition. You can also use pterostilbene for a more direct activation.

[Bryan_S]

Without rummaging through this entire thread hasn't it been shown that taking nicotinamide riboside does not in fact inhibit SIRT1 and that it activates it? If so, doesn't that tell us something about its dropping the ribose before entering muscular tissue? If nicotinamide on its own inhibits SIRT1 and NR activates it, then this is either not true or something is amiss here.  Because if it were converted to NAM before reaching the targeted area, then wouldn't it inhibit SIRT1?

 

It does take some rummaging but most of the story is here somewhere. We have a special search tool for that in the upper right hand corner of your screen and its how I located the following.

 

What your seeking is information on the Nicotinamide binding pockets. These pockets aid in disabling the enzymes as part of the feedback loop. When concentrations of Nicotinamide get high enough the SIRT molecules themselves can be disabled just by the accumulation of NAM. They have a built in pocket that accepts the Nicotinamide molecule and this inactivates them as part of the feedback loop.

 

http://www.longecity...-11#entry740748

 

So if you take NAM for instance one of the first things that will happen as it is taken up in cells is you'll silence your already circulating sirtuins in your protoplasm. At some point once the NAM is converted to NMN by your NAMPT the resulting NAD will help stimulate more SIRT production until there is enough to overcome the initial inhibition. NR taking a different path doesn't initially silence your sirtuins and the increasing NAD helps stimulate the production of more sirtuins. This is one of the major differences in the 2 precursors. NR doesn't fit into the binding pocket and NAM does.

[Nate-2004]

 

Without rummaging through this entire thread hasn't it been shown that taking nicotinamide riboside does not in fact inhibit SIRT1 and that it activates it? If so, doesn't that tell us something about its dropping the ribose before entering muscular tissue? If nicotinamide on its own inhibits SIRT1 and NR activates it, then this is either not true or something is amiss here.  Because if it were converted to NAM before reaching the targeted area, then wouldn't it inhibit SIRT1?

 

It does take some rummaging but most of the story is here somewhere. We have a special search tool for that in the upper right hand corner of your screen and its how I located the following.

 

What your seeking is information on the Nicotinamide binding pockets. These pockets aid in disabling the enzymes as part of the feedback loop. When concentrations of Nicotinamide get high enough the SIRT molecules themselves can be disabled just by the accumulation of NAM. They have a built in pocket that accepts the Nicotinamide molecule and this inactivates them as part of the feedback loop.

 

http://www.longecity...-11#entry740748

 

So if you take NAM for instance one of the first things that will happen as it is taken up in cells is you'll silence your already circulating sirtuins in your protoplasm. At some point once the NAM is converted to NMN by your NAMPT the resulting NAD will help stimulate more SIRT production until there is enough to overcome the initial inhibition. NR taking a different path doesn't initially silence your sirtuins and the increasing NAD helps stimulate the production of more sirtuins. This is one of the major differences in the 2 precursors. NR doesn't fit into the binding pocket and NAM does.

 

 

I understand that much as far as the theory goes but has this been tested to see if that's what is actually happening in vivo? Is SIRT being activated rather than inhibited by NR? He's saying that NR breaks down into NAM first which would mean that NAM would aid in disabling the enzymes as you describe and as the graphic you link illustrates, if that in fact is what is happening. I apologize if I'm totally not getting this.

[Bryan_S]

Nate-2004,

 

Yes this has been tested, run Nicotinamide binding pockets as a google search and skim the results. This is one mechanism of the SIRT inhibition. You hit on the point earlier if NR is being broken down into NAM first before cell absorption you would see the inhibition of the SIRT's initially but thats not what's been shown overall across multiple studies.

http://www.ncbi.nlm....pubmed/25470550

http://www.ncbi.nlm....les/PMC3616313/

http://www.ncbi.nlm....les/PMC3805877/

 

 

Then see what SIRT results you get on NAM Nicotinamide. This argument that NR is broken down into NAM is getting old. I'm sure some does but not enough to inhibit the Sirtuin's. The proof is NAM inhibits them right off and NR doesn't.

 

 

[Nate-2004]

Thanks Bryan, super informative answer. 

 

Side note: Of course I was ill informed, that's why I was asking the question. Not sure who marked my question with that but seems unnecessary.

 

 

[Tom Andre F. (ex shinobi)]

 

 

Side note: Of course I was ill informed, that's why I was asking the question. Not sure who marked my question with that but seems unnecessary.

 

Lol I dont understand some notation too :

 

I got 2 off topic (?) and 1 unfriendly (?!) for instance in a post where I explained why pterostilbene probably does not increase sirt1 activity in ALZ (because we need actually the opposite) here : http://www.longecity...or/#entry782130

 

and I got some disagree above while I explained the cell study. I think its better to just ignore

Edited by Tom Andre F. (ex shinobi), 13 August 2016 - 08:41 PM.

[Junk Master]

Great thread!  Just had to chime in that Aicar has been known to the athletic community for a few years and is widely available at most peptide sites.  It is usually stacked with GW-501516 (Cardarine) by extreme endurance athletes, or by bodybuilders in cutting phases.  I could list a dozen semi-reputable sources but you doubtlessly could find them yourselves.

 

At one point, it was being billed as an "exercise pill," but as is so often the case that didn't turn out to be true.

 

I have no experience with the chemical but I believe it to be of marginal value except to those athletes recovering from injury.  For sure, it offers no bang for yur buck compared to EPO.  

 

A more interesting chem IMO is ITTP compounded with beta cyclodextrin, for endurance athletes, that is.

[Bryan_S]

Muscle Decline in Mice Caused by Lowered Mitochondrial Factor Could Improve MD Treatment

 

 AUGUST 15, 2016 Magdalena Kegel

 

http://mitochondrial...ular-dystrophy/

 

“At first, we were surprised by how rapidly NR was able to reactivate dormant mitochondria in muscle, despite being largely consumed by other cell types,” said David Frederick, PhD, a postdoctoral fellow in Baur’s lab. “It appears that a relatively small enhancement in muscle NAD can have profound functional consequences in this setting.”

[Bryan_S]

It takes two to tango: NAD+ and sirtuins in aging/longevity control

 

http://www.nature.co...es/npjamd201617

Review Article | OPEN Article

Shin-ichiro Imai & Leonard Guarente

 

Abstract

The coupling of nicotinamide adenine dinucleotide (NAD+) breakdown and protein deacylation is a unique feature of the family of proteins called ‘sirtuins.’ This intimate connection between NAD+ and sirtuins has an ancient origin and provides a mechanistic foundation that translates the regulation of energy metabolism into aging and longevity control in diverse organisms. Although the field of sirtuin research went through intensive controversies, an increasing number of recent studies have put those controversies to rest and fully established the significance of sirtuins as an evolutionarily conserved aging/longevity regulator. The tight connection between NAD+ and sirtuins is regulated at several different levels, adding further complexity to their coordination in metabolic and aging/longevity control. Interestingly, it has been demonstrated that NAD+ availability decreases over age, reducing sirtuin activities and affecting the communication between the nucleus and mitochondria at a cellular level and also between the hypothalamus and adipose tissue at a systemic level. These dynamic cellular and systemic processes likely contribute to the development of age-associated functional decline and the pathogenesis of diseases of aging. To mitigate these age-associated problems, supplementation of key NAD+ intermediates is currently drawing significant attention. In this review article, we will summarize these important aspects of the intimate connection between NAD+ and sirtuins in aging/longevity control.

[Bryan_S]

Of mice and muscles: How do athletes endure their grueling runs, swims, and rides?

 

https://www.scienced...60817171826.htm

Date: August 17, 2016

Source: Perelman School of Medicine at the University of Pennsylvania

Summary: As the Rio Olympic Games continue, many armchair spectators of the Games may be wondering: How do those athletes endure their grueling runs, swims, and rides?

 

Penn has a long history of muscle research, much of which is relevant to Olympic-level athletes and their abilities. As the Rio Olympic Games approach, many armchair spectators of the Games may be wondering: How do those athletes endure their grueling runs, swims, and rides? And, on the flip side -- if their achievements seem too good to be true -- are anti-doping officials able to tell what attributes are due to nature or off-the-books nurture?

[Nate-2004]

 

It takes two to tango: NAD+ and sirtuins in aging/longevity control

 

http://www.nature.co...es/npjamd201617

Review Article | OPEN Article

Shin-ichiro Imai & Leonard Guarente

 

Abstract

The coupling of nicotinamide adenine dinucleotide (NAD+) breakdown and protein deacylation is a unique feature of the family of proteins called ‘sirtuins.’ This intimate connection between NAD+ and sirtuins has an ancient origin and provides a mechanistic foundation that translates the regulation of energy metabolism into aging and longevity control in diverse organisms. Although the field of sirtuin research went through intensive controversies, an increasing number of recent studies have put those controversies to rest and fully established the significance of sirtuins as an evolutionarily conserved aging/longevity regulator. The tight connection between NAD+ and sirtuins is regulated at several different levels, adding further complexity to their coordination in metabolic and aging/longevity control. Interestingly, it has been demonstrated that NAD+ availability decreases over age, reducing sirtuin activities and affecting the communication between the nucleus and mitochondria at a cellular level and also between the hypothalamus and adipose tissue at a systemic level. These dynamic cellular and systemic processes likely contribute to the development of age-associated functional decline and the pathogenesis of diseases of aging. To mitigate these age-associated problems, supplementation of key NAD+ intermediates is currently drawing significant attention. In this review article, we will summarize these important aspects of the intimate connection between NAD+ and sirtuins in aging/longevity control.

 

 

A good review from Nature, that's encouraging.

[Harkijn]

The article mentions that NAMPT activity peaks in the early afternoon, so I suppose it can be argued that we should prevent low availability of NAD+ by taking NR   in the late morning.

[tunt01]

Imai, Guarante 2016 looks a lot like their 2014 Review.  Anyone happen to know any differences before I invest my time reading it?

[Nate-2004]

The article mentions that NAMPT activity peaks in the early afternoon, so I suppose it can be argued that we should prevent low availability of NAD+ by taking NR   in the late morning.

 

Why late in the morning? What does it mean when NAMPT activity peaks?

[Harkijn]

 

The article mentions that NAMPT activity peaks in the early afternoon, so I suppose it can be argued that we should prevent low availability of NAD+ by taking NR   in the late morning.

 

Why late in the morning? What does it mean when NAMPT activity peaks?

 

Nate, these thoughts are just layman's thinking, just meant to spark  some digestion of this complex subjectmatter.  NAMPT produces NAD+ and has peak  activity in the early afternoon, says Guarente. At that moment it will need a lot of NR (or NMN) to make NAD+ with, I think. So, allowing for some absorption time, I reasoned that some extra NR should be taken shortly before peak NADproduction. Putting it reversely: NAMPT will only be able to produce the amount of NAD+ which you need in sofar as NR is available. A daily deficit is what we call aging...

Of course, I realize there are countless other aspects to NAD+ production.

[Nate-2004]

 

 

The article mentions that NAMPT activity peaks in the early afternoon, so I suppose it can be argued that we should prevent low availability of NAD+ by taking NR   in the late morning.

 

Why late in the morning? What does it mean when NAMPT activity peaks?

 

Nate, these thoughts are just layman's thinking, just meant to spark  some digestion of this complex subjectmatter.  NAMPT produces NAD+ and has peak  activity in the early afternoon, says Guarente. At that moment it will need a lot of NR (or NMN) to make NAD+ with, I think. So, allowing for some absorption time, I reasoned that some extra NR should be taken shortly before peak NADproduction. Putting it reversely: NAMPT will only be able to produce the amount of NAD+ which you need in sofar as NR is available. A daily deficit is what we call aging...

Of course, I realize there are countless other aspects to NAD+ production.

 

 

That makes sense to me. I dunno if other more knowledgeable people can comment. I wonder how your body knows what time it is. Is it based on when you wake up? I generally wake up at 9am every day.  Strange that it's in the early afternoon. I wonder if that's related to the cortisol your body produces around the same time, 1-2pm, they say it's better to drink coffee after 2 and not during that time and that your body produces cortisol as soon as you wake up for about 50 mins as well. I wonder if there's another spike in NAMPT around that time.

[Bryan_S]

Imai, Guarante 2016 looks a lot like their 2014 Review.  Anyone happen to know any differences before I invest my time reading it?

 

 

Received: 25 January 2016 Revised: 15 May 2016 Accepted: 17 May 2016 Published online: 18 August 2016   Appears different to me and the submission dates tell the story.

[playground]

Thanks to everyone in this thread for contributing so much

research work, opinion, speculation and argument to this topic.  It's valuable.

 

So...  In the spirit of reciprocity ...I'd like to  share with you the results of my own research...

by giving you all the name of a  free-access-to-research-papers  website

It is:  

 

  sci-hub.cc

 

previously this website was called sci-hub.net, and then sci-hub.io,  currently it's sci-hub.cc.

If this website stops working in the future it's probably changed it's domain to sci-hub.xyz

(or something similar) 

 

How to use it  ?

 

Here's an example of a hidden paper.

 

Why NAD+ Declines during Aging:  It's Destroyed.

 

This is a june 2016 paper by Schultz and Sinclair.

 

 

Unless you have access to academic papers this article hidden behind a pay wall.

 

So to get this paper for free do the following:

1.  Go to www.sci-hub.cc

2.  paste the article title into the search bar.. and a few seconds later .. . voila !

 

     http://sci-hub.cc/10...met.2016.05.022

 

And there you have it. 

You can download the pdf from that URL... or you can read it online if you prefer

the save a tropical forest.

 

 

More information:

 

More info about library genesis can be found here : 

 

      https://sites.google...library-genesis

 

All I know is... that sci-hub.cc is a front end to a larger database of world wide

research papers called Library Genesis. (LibGen).

 

I don't know of any other front ends to this database.  Do you ?

 

I don't know of any other websites offering access to articles otherwise hidden

behind a pay wall or otherwise denied access to the public.  Do you ?

Edited by playground, 20 August 2016 - 01:59 PM.

[Harkijn]

Thanks to everyone in this thread for contributing so much

research work, opinion, speculation and argument to this topic.  It's valuable.

 

So...  In the spirit of reciprocity ...I'd like to  share with you the results of my own research...

by giving you all the name of a  free-access-to-research-papers  website

It is:  

 

  sci-hub.cc

 

previously this website was called sci-hub.net, and then sci-hub.io,  currently it's sci-hub.cc.

If this website stops working in the future it's probably changed it's domain to sci-hub.xyz

(or something similar) 

 

How to use it  ?

 

Here's an example of a hidden paper.

 

Why NAD+ Declines during Aging:  It's Destroyed.

 

This is a june 2016 paper by Schultz and Sinclair.

 

 

Unless you have access to academic papers this article hidden behind a pay wall.

 

So to get this paper for free do the following:

1.  Go to www.sci-hub.cc

2.  paste the article title into the search bar.. and a few seconds later .. . voila !

 

     http://sci-hub.cc/10...met.2016.05.022

 

And there you have it. 

You can download the pdf from that URL... or you can read it online if you prefer

the save a tropical forest.

 

 

More information:

 

More info about library genesis can be found here : 

 

      https://sites.google...library-genesis

 

All I know is... that sci-hub.cc is a front end to a larger database of world wide

research papers called Library Genesis. (LibGen).

 

I don't know of any other front ends to this database.  Do you ?

 

I don't know of any other websites offering access to articles otherwise hidden

behind a pay wall or otherwise denied access to the public.  Do you ?

Thanks, Playground for pointing to this article. When it was mentioned before (by me :-) ) it mainly drew criticism because of Sinclair's reserved attitude towards NR. Still, for those of us who  try to educate ourselves in molecular biology via Longecity it is a very clear summary of what happens after NAD+ is produced.

[albedo]

Views shared by Leonard Guarente on the Cell Symposium on Aging and Metabolism of July 10–12 in Spain (http://www.cell-symp...metabolism.com/):

 

"The discovery that the anti-aging proteins, sirtuins, are NAD+-dependent deacylases suggested an intimate nexus between metabolism and aging. Studies in a variety of organisms indicate that NAD+ levels and the activity of sirtuins decline during aging, and supplementation with NAD+ precursors (nicotinamide riboside and nicotinamide mononucleotide) can raise NAD+ levels in old animals. This is associated with improved mitochondrial function, health benefits, and longer lifespan in worms and mice. When tested, these effects required the activity of sirtuins. Will the NAD+/sirtuin axis prove to be important in human health maintenance? Intervention studies are critical from a science standpoint, because other data have been uninformative or equivocal regarding any role in human aging of genetic pathways that emerged from lower organisms. In addition to NAD+ precursors, sirtuin activators are in development at GSK, and TOR inhibitors (rapamycin and its derivatives) are candidates for human trials. Metformin, which has a long and stellar history in the diabetes field, has also been proposed. Why haven’t still more compounds emerged from the field of aging research? The science is still in its adolescence and, in the case of human aging, perhaps its infancy. We may have taken but a first step in a long journey. It is nonetheless amazing that one very promising path leads to a ubiquitous small molecule that is fundamental to life and known for more than a century."

http://www.cell.com/...4131(16)30239-X

 

See also the full list:

http://www.cell.com/...(16)30239-X.pdf