2255 replies to this topic

[stefan_001]

 

 

 

Apologies to everyone in advance as I'm far from being an expert in field of longevity, but I've trying to educate myself through lotta lurking and reading.

As I skimmed the whole Samuel A.J. trammel's papers and the following statements caught my eyes.

"The ability of milk to bind and preserve the integrity of NR makes dairy products potentially good sources of supplementing NR along with, specially non organic sources"

Will it be advisable to chug down a glass of milk along with NR? As we want it to reach our gut as stable as possible , even though I was recommended by HPN's owner Sean Torbati to avoid fats while taking NR.


"Though current data is highly suggestive that NMN utilization requires dephosphorylation by CD73 to NR or hydrolysis to Nam by CD38"

If CD38 is involved in the process of NMN =>>NAM, why does it get outta hand with age? Will it be such a good idea to inhibit it for the long run as we don't know the role that it plays? What about keeping their levels to a youth stage, so it does what it suppose to do?

CD38 has been implicated in the secretion and function of hormones such as oxytocin and ACTH and may modulate maternal and social behavior and also CD38 plays a key role in the mechanism by which the organism fights bacterial infection... And God knows what else...

Cuz some people are supplementing with quercetin and this is being identified as a Sirt 1 inhibitor along with CD38.In fact, SIRT1 and CD38 have several similarities in their enzymatic and catalytical properties.

http://www.ncbi.nlm....les/PMC2883294/

Wouldn't it be better to use. Apigenin over quercetin?http://www.ncbi.nlm....pubmed/23172919


"NMN depends upon CD38, CD73, and NRK"

Will this explain why Sinclair was able to bring the clock back on those old mice's muscles in such short period of time? I'm guessing that old mouse had high levels of CD38

Because according to the paper it shows that NR superior than NMN and yet we have not seen the results of NMN had in such short period of time.

"NR contributed to the intracellular NAD metabolome more rapidly than NMN and increased NAD+ by more than 2 fold after 24 hours, indicating NR is kinetically superior to NMN"

Regarding the discussion between Bryan and Tom, it looks like NR is superior to NA and NAM at hepatic levels even though NA produced the least increase in hepatic NAD+ but also was 4-6 hours faster than NR and Nam in the kinetics of hepatic NAD+ accumulation. They also used NAAD as biomarker to state that NR is superior , but what's the role of NAAD , is it a pool to raise NAD+ over time?

NR is a superior liver precursor to NAD+ compared to Nam and NA and the increase in NAD+ correlated with NAAD... But is it that superior?


Thoughts?

Torbati advised you to avoid eating fat and NR at the same time. Did he give you a reason for this?Perhaps a reference?

Would love to know the answer to this one.

I'd luv to know the answers to all of that.... As per Torbati , I wrote him an e-mail regarding my homocysteine levels ; asking him if he knew any relationship between high levels of HCY and NR intake and he replied back telling me he didn't have any knowledge about it and to avoid fats while taking g NR, NO references provided!

Honestly speaking I'm doing opposite ( healthy fats though) ramping up my fat intake while ditching most of the unhealthy carbs.

Btw I've found the email, I've attached a screenshot of it, I was also asking him about taking it subligually

 

 

"If CD38 is involved in the process of NMN =>>NAM, why does it get outta hand with age? Will it be such a good idea to inhibit it for the long run as we don't know the role that it plays? What about keeping their levels to a youth stage, so it does what it suppose to do?"

 

My thinking on this one is:that CD38 is not rate limiting in the process and the fact that it is much lower at a younger age supports the idea that the high levels are not needed at leastt for the metabolism.

[Bryan_S]

 

"If CD38 is involved in the process of NMN =>>NAM, why does it get outta hand with age? Will it be such a good idea to inhibit it for the long run as we don't know the role that it plays? What about keeping their levels to a youth stage, so it does what it suppose to do?"

 

My thinking on this one is:that CD38 is not rate limiting in the process and the fact that it is much lower at a younger age supports the idea that the high levels are not needed at leastt for the metabolism.

 

My thought as well. There is something else driving it, and when that is discovered maybe, just maybe we can get a handle on that. Some feel it involves senescent cells and the rise in CD38 does follow their accumulation. By the same token if senescent cells are uncontrollably producing CD38 Nicotinamide Riboside in mice has been shown to slow down cells from entering this state even reverting some cells. We had some interesting comments follow this announcement on fertility.

 

NAD⁺ repletion improves mitochondrial and stem cell function and enhances life span in mice.

http://www.ncbi.nlm....pubmed/27127236

 

Abstract

Adult stem cells (SCs) are essential for tissue maintenance and regeneration yet are susceptible to senescence during aging. We demonstrate the importance of the amount of the oxidized form of cellular nicotinamide adenine dinucleotide (NAD(+)) and its effect on mitochondrial activity as a pivotal switch to modulate muscle SC (MuSC) senescence. Treatment with the NAD(+) precursor nicotinamide riboside (NR) induced the mitochondrial unfolded protein response and synthesis of prohibitin proteins, and this rejuvenated MuSCs in aged mice. NR also prevented MuSC senescence in the mdx (C57BL/10ScSn-Dmd(mdx)/J) mouse model of muscular dystrophy. We furthermore demonstrate that NR delays senescence of neural SCs and melanocyte SCs and increases mouse life span. Strategies that conserve cellular NAD(+) may reprogram dysfunctional SCs and improve life span in mammals.

[playground]

To quote Black Fox:

 

Wouldn't it be better to use. Apigenin over quercetin?   http://www.ncbi.nlm....pubmed/23172919

 

 

Thanks Black Fox for bringing my attention to apigenin.

 

 

If Apigenin inhibits CD38, then perhaps it's worth supplementation.

Who knows ? 

Introspection may give us some clues.... 

More energy, less energy, better stamina, better concentration, more enthusiasm etc etc.

CD38 may turn out to be a key chemical  (to aid an understanding of this jigsaw puzzle).

 

apigenin is available in camomile extract -- So It's already available as a supplement.

 

apigenin has certain virtues that make it attractive even beyond it's CD38 effects:

(1)  It induces autophagy

(2)  It induces neurogenesis, in vitro and in vivo

(source:  https://en.wikipedia.../wiki/Apigenin)

 

for example:  This camomile extract (link below) is 1.2%  apigenin.  

That doesn't sound like a lot.  

 

What's a standard (CD38-inhibiting) dose of apigenin ?

 

http://www.ebay.co.u...z0AAOSwqBJXUHqa

 

I also found this:  Which is reputedly 98% pure apigenin...

 

http://www.ebay.co.u...3PRyfrYIkz8L4fQ

 

I want some, this might be an effective way of getting more mileage

out of our NR+.

 

But i don't know what an appropriate or effective dose of apigenin would be. 

Does anyone know ?  Educated speculations welcome.

 

The only sources of apigenin that i'm aware of are on ebay.

Does anyone have other sourcing suggestions ?

 

Thanks to  anyone that responds :-)

 

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

post script:

a dose of 100mg of apigenin is suggested on this thread:

http://www.longecity...in-experiences/

 

It seems swansons sells 50mg apigenin tablets

http://www.swansonvi...n-50-mg-90-caps

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

 

Edited by playground, 25 September 2016 - 05:04 AM.

[playground]

 

Btw I've found the email, I've attached a screenshot of it, I was also asking him about taking it subligually

 

 

Torbati advised you to stop eating fat and NR at the same time.  Did he give a reason for this ?  Perhaps a reference ?

 

 

My question is:   Are there any substances at all (vitamins, minerals, amino acids, proteins etc)

whose absorption is blocked by the presence of fats/oils ?

 

Is this suggestion nonsense, or might there be, perhaps unpublished, research demonstating

that a high fat meal would interfere with the oral absorption of NR+  ?

 

 

[Bryan_S]

Guys I'm going to ask that we not publish personal messages. Especially those contains personal contact information. Sean was pretty neutral about sublingual and I haven't heard of a high fat meals interfering with NR absorption.

[stefan_001]

"If CD38 is involved in the process of NMN =>>NAM, why does it get outta hand with age? Will it be such a good idea to inhibit it for the long run as we don't know the role that it plays? What about keeping their levels to a youth stage, so it does what it suppose to do?"

My thinking on this one is:that CD38 is not rate limiting in the process and the fact that it is much lower at a younger age supports the idea that the high levels are not needed at leastt for the metabolism.

My thought as well. There is something else driving it, and when that is discovered maybe, just maybe we can get a handle on that. Some feel it involves senescent cells and the rise in CD38 does follow their accumulation. By the same token if senescent cells are uncontrollably producing CD38 Nicotinamide Riboside in mice has been shown to slow down cells from entering this state even reverting some cells. We had some interesting comments follow this announcement on fertility.

NAD⁺ repletion improves mitochondrial and stem cell function and enhances life span in mice.
http://www.ncbi.nlm....pubmed/27127236

Abstract
Adult stem cells (SCs) are essential for tissue maintenance and regeneration yet are susceptible to senescence during aging. We demonstrate the importance of the amount of the oxidized form of cellular nicotinamide adenine dinucleotide (NAD(+)) and its effect on mitochondrial activity as a pivotal switch to modulate muscle SC (MuSC) senescence. Treatment with the NAD(+) precursor nicotinamide riboside (NR) induced the mitochondrial unfolded protein response and synthesis of prohibitin proteins, and this rejuvenated MuSCs in aged mice. NR also prevented MuSC senescence in the mdx (C57BL/10ScSn-Dmd(mdx)/J) mouse model of muscular dystrophy. We furthermore demonstrate that NR delays senescence of neural SCs and melanocyte SCs and increases mouse life span. Strategies that conserve cellular NAD(+) may reprogram dysfunctional SCs and improve life span in mammals.

Yes that was an interesting study. I am somewhat hypothizing that the game is rigged against us. My thinking is that when we grow into adulthood the balance of processes tilts us into the downward cycle. Probably there is no permanent fix. The only way is to control it as much as possible. Best outcome might be that with heavy supplementation we fix the largest offenders and then could continue with a lower maintenance dose but never stop entirely. We could really use an easy test to measure NAD+ and other factors like a diabetes glucose meter.

[Bryan_S]

The studies I've read on worms suggests once sexual maturity is reached the protective cellular mechanisms along with growth begins to ramp down. Its more like throttling down systems to protect resources for the long haul. They mention a genetic switch is flipped. The more I read the more I think of us more as vehicles to protect and feed our germ cells because thats where our immortality resides. Within us resides a cell line going back millions of years. Now if generations of women had children later and later in life this would make a difference. Studies on short lived insects and mammals have demonstrated this principal. With women waiting later in life to have children because of careers in western nations this may already be happening.

 

Here was a post on the topic some time ago

 

 

Repression of the Heat Shock Response Is a Programmed Event at the Onset of Reproduction

http://www.cell.com/...2765(15)00499-2

 

[malbecman]

Cell Metab. 2016 Aug 9;24(2):269-82. doi: 10.1016/j.cmet.2016.07.005.

Loss of NAD Homeostasis Leads to Progressive and Reversible Degeneration of Skeletal Muscle.

Frederick DW1, Loro E2, Liu L3, Davila A Jr1, Chellappa K1, Silverman IM4, Quinn WJ 3rd1, Gosai SJ4, Tichy ED5, Davis JG1, Mourkioti F5, Gregory BD4, Dellinger RW6, Redpath P7, Migaud ME7, Nakamaru-Ogiso E8, Rabinowitz JD3, Khurana TS2, Baur JA9.

Author information

    Abstract

NAD is an obligate co-factor for the catabolism of metabolic fuels in all cell types. However, the availability of NAD in several tissues can become limited during genotoxic stress and the course of natural aging. The point at which NAD restriction imposes functional limitations on tissue physiology remains unknown. We examined this question in murine skeletal muscle by specifically depleting Nampt, an essential enzyme in the NAD salvage pathway. Knockout mice exhibited a dramatic 85% decline in intramuscular NAD content, accompanied by fiber degeneration and progressive loss of both muscle strength and treadmill endurance. Administration of the NAD precursor nicotinamide riboside rapidly ameliorated functional deficits and restored muscle mass despite having only a modest effect on the intramuscular NAD pool. Additionally, lifelong overexpression of Nampt preserved muscle NAD levels and exercise capacity in aged mice, supporting a critical role for tissue-autonomous NAD homeostasis in maintaining muscle mass and function. 

Copyright © 2016 Elsevier Inc. All rights reserved.

PMID:   27508874

 

Edited by malbecman, 26 September 2016 - 06:11 PM.

[Bryan_S]

Maternal serum levels of nicotinamide linked to child’s risk of atopic eczema

http://www.news-medi...pic-eczema.aspx

[Nate-2004]

Maternal serum levels of nicotinamide linked to child’s risk of atopic eczema

http://www.news-medi...pic-eczema.aspx

 

Interesting, I wonder if that applies to NR as well.

[Bryan_S]

 

Maternal serum levels of nicotinamide linked to child’s risk of atopic eczema

http://www.news-medi...pic-eczema.aspx

 

Interesting, I wonder if that applies to NR as well.

 

 

Considering NR gets turned into NMN then NAD what's NAD turned into after its depleted?

 

These precursors can give different benefits when first consumed but are recycled on the second pass as nicotinamide.

[albedo]

Looking at some genetics aspects, the SelfHacked site mentions (bold mine):

 

“SelfDecode has the NAMPT gene, which controls NAD+ levels.  If your genes are not producing NAMPT as well, that would suggest that you’ll have a higher need for NR. Check out your SNPs (need 23andme or other genetic service to then sign up):

RS1319501 (NAMPT)

RS9770242 (NAMPT)

NAD(+) level decrease in aged mice and humans, which is a result of lower NAMPT ®.” (1)

 

This study gives a more complete picture of the genetics studies:

 

“…The visfatin/PBEF gene consists of 11 exons and 10 introns spanning 34.7-kb and is located on chromosome 7q22.2. Few studies of polymorphic markers in the visfatin gene have been reported to date. Bottcher et al. [37] did not find any association with either T2DM, in a cohort of 503 diabetic subjects and 476 healthy controls, or with T2DM-related traits in 626 non-diabetic subjects from Germany. However, they found an association between the -948 G > T single-nucleotide polymorphism (SNP) and fasting insulin levels in non-diabetic subjects (p < 0.05). The ratio of visceral/subcutaneous visfatin mRNA expression was associated with all three genetic polymorphisms studied (rs9770242, -948G > T, rs4730153).

To investigate the role of visfatin gene variants in obesity-related phenotypes, Bailey et al. [38] genotyped a total of 13 SNPs in the promoter region of the gene in 918 participants from 208 families evaluated in the Quebec Family Study. A significant association was found between two SNPs (rs9770242 and rs1319501) and fasting insulin levels (p = 0.002). These SNPs were also associated with fasting glucose (p = 0.02). Furthermore, they found that a more distal SNP (rs7789066) was significantly associated with the apolipoprotein B component of VLDL (p = 0.012).

Zhang et al. [39] studied a group of 814 white patients from the USA and a group of non-diabetic controls (n = 320). They found a significant association between -948C > A and T2DM (p = 0.021). In a non-diabetic population (n = 630), the same -948C allele that conferred increased risk of T2DM was significantly associated with higher plasma levels of fibrinogen and C-reactive protein (p = 0.0022 and 0.0038, respectively). However, no significant associations were observed with BMI, waist circumference, serum glucose levels, or fasting insulin levels. They suggested that the visfatin gene may play a role in determining T2DM susceptibility, possibly by modulating chronic, low-grade inflammatory responses.

Korner et al. [40] studied 731 schoolchildren and an independent cohort of 167 obese children from Germany. They genotyped 3 SNPs (rs9770242, -948G > T, rs4730153). The authors did not find association of any of the 3 polymorphisms or their haplotypes with BMI, waist-to-hip ratio, glucose, insulin, or lipid levels. However, the -948G variant was associated with significantly higher diastolic blood pressure in obese children (p < 0.05 after adjusting for age, sex, pubertal stage, and height).

Blakemore et al. [41] studied 1,709 severely obese subjects together with 2,367 T2DM individuals and 2,850 controls. For quantitative trait analysis, an additional 2,362 subjects were typed for rs10487818 from a general population sample. This rare SNP, rs10487818, located in intron 4, was associated with protective effect against severe obesity. This is one of the first rare SNPs shown to be protective against a common polygenic disease like obesity and provides further evidence that rare alleles of strong effect can contribute to this kind of complex diseases.

More recently, Yan et al. [42] suggested that Visfatin -1535C > T polymorphism might be associated with reduced risk of CAD in a Chinese population. There was a significant association between Visfatin -1535C > T polymorphism and triglyceride levels in both CAD patients and controls (p = 0.003). In non diabetic Japanese subjects, Tokunaga et al. [43] found that the -1535T/T genotype modulates lipid levels promoting lower serum triglyceride levels and higher HDL-cholesterol levels. In this investigation, reporter gene assay of 3T3-L1 adipocytes revealed that the promoter activity of -1535T and -1535C was similar, suggesting that the observed association may reflect linkage disequilibrium between -1535T > C and other causative variations of the visfatin gene.

Taken together, these studies suggest that genetic variants in the Visfatin gene can be associated with some phenotypes related to glucose, lipids, and other metabolic and vascular traits. Further studies in other populations must be carried out to better clarify these points…” (2)

 

NAMPT looks, as everything related to metabolism, a complex issue with up and down sides (e.g. pro-inflammatory in its extra cellular form). The Part 5 of the huge NAD blog by Jim Watson tries to tackle this:

 

“…But then, a dark side of all of this begin to emerge as it was realized that NAMPT has long been known to be a traveler using various aliases, especially outside of cells where it did shocking things. NAMPT was often behaving inappropriately for its princely role when it is outside our cells.   Not to be trusted, extra-cellular NAMPT (eNAMPT) can be caught creating horrible inflammation and is closely associated with highly disreputable diseases.  Oozing out of fat cells and helping create colorectal cancer is not politically correct for a supposedly good guy. The same is true for destroying cartilage in both osteo and rheumatoid arthritis.  We have written before about the good side of NAMPT when it is in cells.  This present blog entry is an expose of the bad inflammation-generating side of eNAMPT.  And, it turns out that eNAMPT is not completely bad, after all.” (3)

 

(1) Top 9 Health Benefits of Nicotinamide Riboside

https://selfhacked.c...amide-riboside/

 

(2) Visfatin, glucose metabolism and vascular disease: a review of evidence

https://www.ncbi.nlm...les/PMC2857825/

 

(3) Part 5 of the NAD world: the conflicting roles of NAMPT – inflammation or rescue? Also Part 1 on a new series on inflammation

http://www.anti-agin...n-inflammation/

 

[maximum411]

Does anyone have any insight as to whether NR or NMN would make a more effective supplement (ignoring the price discrepancy)? I have read in at least one paper that NR is the form that actually enters cells.

[Bryan_S]

Does anyone have any insight as to whether NR or NMN would make a more effective supplement (ignoring the price discrepancy)? I have read in at least one paper that NR is the form that actually enters cells.

 

Correct as far as the studies have indicated. If it were cheaper than NR it might be a consideration but it appears it is broken down at the cell membrane and enters as NR. 

[Bryan_S]

NAMPT-Mediated NAD+ Biosynthesis Is Essential for Vision In Mice

http://www.cell.com/...1247(16)31169-X

 

Jonathan B. Lin6, Shunsuke Kubota6, Norimitsu Ban, Mitsukuni Yoshida, Andrea Santeford, Abdoulaye Sene, Rei Nakamura, Nicole Zapata, Miyuki Kubota, Kazuo Tsubota, Jun Yoshino, Shin-ichiro ImaicorrespondencePress enter key for correspondence informationemailPress enter key to Email the author, Rajendra S. Apte7,correspondencePress enter key for correspondence informationemailPress enter key to Email the author

6Co-first author

7Lead Contact

Open Access

DOI: http://dx.doi.org/10...rep.2016.08.073

 

 

Highlights

 

• •Rod or cone photoreceptor-specific deletion of Nampt causes retinal degeneration
• •Mouse models of retinal dysfunction exhibit early retinal NAD+ deficiency
• •SIRT3/SIRT5 is important for NAD+-dependent retinal homeostasis
• •NAD+ deficiency causes metabolic dysfunction and SIRT3 dysfunction

 

[bluemoon]

 

Does anyone have any insight as to whether NR or NMN would make a more effective supplement (ignoring the price discrepancy)? I have read in at least one paper that NR is the form that actually enters cells.

 

Correct as far as the studies have indicated. If it were cheaper than NR it might be a consideration but it appears it is broken down at the cell membrane and enters as NR. 

 

 

But Sinclair said in the video above (I think - maybe another place) that "they" are trying to bring the cost of NMN down with a new manufacturing method. If successful, competition could force the price of NR down a bit as well. Should buyers be indifferent to taking NR or NMN? And then we can expect the pharmaceuticals to enter the fray.  

[Harkijn]

Do you want to put your expensive NR to the best possible use and are you not daunted by biochemical parlance?

 

Then please read Logic's thread:

 

http://www.longecity...n-by-pathogens/

Apparently, NAD+ is not just consumed by CD38 and PARPS but also by auxotroph pathogens .  Indeed, you might even wonder if upping your NAD+ by taking NR results in extra 'feeding ' your CMV, toxoplasmosis etc.

I am glad that I am a regular consumer of coconut oil......

[stefan_001]

Do you want to put your expensive NR to the best possible use and are you not daunted by biochemical parlance?

 

Then please read Logic's thread:

 

http://www.longecity...n-by-pathogens/

Apparently, NAD+ is not just consumed by CD38 and PARPS but also by auxotroph pathogens .  Indeed, you might even wonder if upping your NAD+ by taking NR results in extra 'feeding ' your CMV, toxoplasmosis etc.

I am glad that I am a regular consumer of coconut oil......

 

I dont agree to this reasoning. NAD+ falls as aging progresses and I cannot recall studies showing that NR can get it back or even close to youthful levels.

[Ukko]

Those mice were injected with NMN.  

 

Is the benefit comparable when regular people are sending NR pills through their GI tract?

 

Don't know. But I used to snort my NR to get a better bang for the buck. And once I snorted niacin (nicotic acid). Weirdest feeling. Felt like a electric wire just went up from my nose to my brain. Super strong reaction. Believe that, as people do with Noopept, snorting NR is the best way to get bang for your buck. But the products now on the market are not pure NR, so you will be snorting fillers too. Which I suppose is fine.

 

Just snort your NR. Just retried snorting like 100mg nicotinic acid. Same reaction. Like a copper wire going up into my brain.
 

Edited by Ukko, 02 October 2016 - 04:37 PM.

[Harkijn]

 

Do you want to put your expensive NR to the best possible use and are you not daunted by biochemical parlance?

 

Then please read Logic's thread:

 

http://www.longecity...n-by-pathogens/

Apparently, NAD+ is not just consumed by CD38 and PARPS but also by auxotroph pathogens .  Indeed, you might even wonder if upping your NAD+ by taking NR results in extra 'feeding ' your CMV, toxoplasmosis etc.

I am glad that I am a regular consumer of coconut oil......

 

I dont agree to this reasoning. NAD+ falls as aging progresses and I cannot recall studies showing that NR can get it back or even close to youthful levels.

 

Stefan, yes NAD+ falls during aging but the million dollar question still is: how? There will be no single cascade leading up to 'aging".  Perhaps this is only one single cascade out of several. The   steady accumulation of CMV, toxoplasmosis and much more over the years seems to sap the NAD+ levels and my point today is that for some people NR might sort of sustain levels of NAD+ ,and that perhaps for others raising NAD+ is temporarily not a good idea! See also the experiences thread.

[Bryan_S]

Of Course raising NAD is a good idea. The only time depleted NAD is good is when your starving the metabolism of cancers while in chemotherapy to get that extra edge. Is there other things at work other than CD38, I believe so, and we know PARP is also another major consumer as are a number of other enzymes. What would be helpful is to show a pie chart showing the consumption of each and graphs showing their consumption over the life of an organism. So I think strategies addressing the major consumers is relevant. I think consumers like our PARP's should be favored because they save off damage from ionizing radiation and oxidative stress, while those producing inflammatory processes need remediation. 

Edited by Bryan_S, 02 October 2016 - 06:04 PM.

[Harkijn]

Of Course raising NAD is a good idea. The only time depleted NAD is good is when your starving the metabolism of cancers while in chemotherapy to get that extra edge. Is there other things at work other than CD38, I believe so, and we know PARP is also another major consumer as are a number of other enzymes. What would be helpful is to show a pie chart showing the consumption of each and graphs showing their consumption over the life of an organism. So I think strategies addressing the major consumers is relevant. I think consumers like our PARP's should be favored because they save off damage from ionizing radiation and oxidative stress, while those producing , processes need remediation. 

Don't ever let your NAD get depleted (or exclusively temporarily as in strenuous exercise). Raising it on a permanent basis however is something which may not always and for everybody be the right thing.

The vast impact which (for instance) CMV has on aging  just might be augmented by comparatively small amounts of NR. No alarm here from me, just pointing out a possible issue of careful consideration.

[Nate-2004]

 

Of Course raising NAD is a good idea. The only time depleted NAD is good is when your starving the metabolism of cancers while in chemotherapy to get that extra edge. Is there other things at work other than CD38, I believe so, and we know PARP is also another major consumer as are a number of other enzymes. What would be helpful is to show a pie chart showing the consumption of each and graphs showing their consumption over the life of an organism. So I think strategies addressing the major consumers is relevant. I think consumers like our PARP's should be favored because they save off damage from ionizing radiation and oxidative stress, while those producing , processes need remediation. 

Don't ever let your NAD get depleted (or exclusively temporarily as in strenuous exercise). Raising it on a permanent basis however is something which may not always and for everybody be the right thing.

The vast impact which (for instance) CMV has on aging  just might be augmented by comparatively small amounts of NR. No alarm here from me, just pointing out a possible issue of careful consideration.

 

 

This is all pretty alarming to me actually. I would definitely like to see a chart of consumption as well.

 

I don't know if I'm infected with CMV or not.

[Supierce]

Of Course raising NAD is a good idea. The only time depleted NAD is good is when your starving the metabolism of cancers while in chemotherapy to get that extra edge. Is there other things at work other than CD38, I believe so, and we know PARP is also another major consumer as are a number of other enzymes. What would be helpful is to show a pie chart showing the consumption of each and graphs showing their consumption over the life of an organism. So I think strategies addressing the major consumers is relevant. I think consumers like our PARP's should be favored because they save off damage from ionizing radiation and oxidative stress, while those producing inflammatory processes need remediation.

SIRT activators like Resveratrol and Pterostilbene also consume NAD+. I wonder if it could be a significant factor.

[Nate-2004]

No the SIRT consumes NAD+ not the activators, but that's the whole point of it all.

[Harkijn]

 

 

Of Course raising NAD is a good idea. The only time depleted NAD is good is when your starving the metabolism of cancers while in chemotherapy to get that extra edge. Is there other things at work other than CD38, I believe so, and we know PARP is also another major consumer as are a number of other enzymes. What would be helpful is to show a pie chart showing the consumption of each and graphs showing their consumption over the life of an organism. So I think strategies addressing the major consumers is relevant. I think consumers like our PARP's should be favored because they save off damage from ionizing radiation and oxidative stress, while those producing , processes need remediation. 

Don't ever let your NAD get depleted (or exclusively temporarily as in strenuous exercise). Raising it on a permanent basis however is something which may not always and for everybody be the right thing.

The vast impact which (for instance) CMV has on aging  just might be augmented by comparatively small amounts of NR. No alarm here from me, just pointing out a possible issue of careful consideration.

 

 

This is all pretty alarming to me actually. I would definitely like to see a chart of consumption as well.

 

I don't know if I'm infected with CMV or not.

 

Nate, CMV is just one example. I posted about pathogens, because we need to take the concerns about NR tendonitis etc. very seriously and this perhaps might be a clue for those afflicted by it. I, too, would like to have more clarity about who 'eats' what.

Side note: you probably are infected with CMV. Most people are. It's been with us since the Stone Age and only gets in full attack if we are undernourished or otherwise frail. However, our immune system is having a lifelong struggle against it. Over the course of the years more and more of our killer T-cells have to specialize in fighting CMV  and therefore there are less and less killer cells available for the fight against other pathogens. A medicine able to eradicate CMV would be a huge step forward towards healthspan and longevity. The Fight Aging blog has a lot of info about CMV.

[Logic]

Here is  a site search for 'CD38 white blood cells immune':

https://cse.google.c...od cells immune

 

It does not take much to put 2 and 2 together and see that CD38 is increased in response to infection.

Further; pathogens that cannot make their own NAD+ (NAD+ auxotrophs) would drain you of your precious intra and extracellular NAD+ causing lower levels of SIRT and PARP etc.

So what Harkijn and I are saying is that while increasing NAD+ is certainly a good idea, one needs to be aware of the fact that pathogens will lead to an increase in NAD+ sapping CD38 or even directly use up your hard gained NAD+ and proliferate in the process..!
IE: A decrease in these pathogens will lead to higher NAD+ levels and a whole lot of other benefits besides. (Inflam-aging etc)

 

Also people with a high NAD+ or NAM/NA/NR/R auxotroph load may react negatively to NR due to these NAD+/NAM/NA/NR stealing pathogens stealing your expensive supp and using it to proliferate long before any gets anywhere where it can do you any good..!

(Candida loves NA and R and probably NR...)
This could explain the negative reaction some people have to NR....

 

Frankly I'm a little worried that this simple thought process has gone right over so many here's heads..!? 

That probably explains the lack of interest in DRACO, SNAPS, Teixobactin, Bavituximab etc and even the easy to find stuff like VCO and Uridine etc...

http://www.longecity...n-by-pathogens/

If you are still hoping that NR is a simple answer to aging that enables you to ignore everything else; now is the time to turn to drink!  

Edited by Logic, 03 October 2016 - 10:08 AM.

[Steve H]

Yes Pathogens and SASP from inflammation are the two main reason NAD+ falls. There is a lot of sense behind the idea that boostng/rejuvenating the immune system would help with this, I know a number of researchers working on doing this as they believe that the immune system decline is a big reason we age. Immune cells clear waste, fight infection and remove senescent cells so it makes sense. MMTP is considering running a project next year that tests rejuvenation of the immune system so we an again look at NAD levels and even combine that approach with senolytics which I have mentioned in videos and articles last year and this year. 

So one cannot simply keep amping up NAD+ as it is going to be diminishing returns. The answer to fix the problem is very likely robust rejuvenation of the immune system combined with periodic senescent cell removal via senolytics to clear out senescent cells missed by the immune system. Our researcher is currently testing macrophage transplants and so far indications are good for lifespan increase, stay tuned.

[Nate-2004]

Wow this is all such a big let down.

 

 

 

Frankly I'm a little worried that this simple thought process has gone right over so many here's heads..!? 

That probably explains the lack of interest in DRACO, SNAPS, Teixobactin, Bavituximab etc and even the easy to find stuff like VCO and Uridine etc...

http://www.longecity...n-by-pathogens/

 

Yeah it's a bit over my head and a lot to take in. I feel like I've wasted all my time, energy and money at this point though I've read and commented on some of those threads. 

 

 

 

If you are still hoping that NR is a simple answer to aging that enables you to ignore everything else; now is the time to turn to drink!

 

I don't think it is a simple one answer solution, but I didn't think it could be feeding into aging.  Turn to drink?

Edited by Nate-2004, 03 October 2016 - 01:58 PM.

[albedo]

 

 

 

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Nate, CMV is just one example. I posted about pathogens, because we need to take the concerns about NR tendonitis etc. very seriously and this perhaps might be a clue for those afflicted by it. I, too, would like to have more clarity about who 'eats' what.

Side note: you probably are infected with CMV. Most people are. It's been with us since the Stone Age and only gets in full attack if we are undernourished or otherwise frail. However, our immune system is having a lifelong struggle against it. Over the course of the years more and more of our killer T-cells have to specialize in fighting CMV  and therefore there are less and less killer cells available for the fight against other pathogens. A medicine able to eradicate CMV would be a huge step forward towards healthspan and longevity. The Fight Aging blog has a lot of info about CMV.

 

 

This brings a little, little, hope. Hell .. why the all area is not progressing faster!

 

IBM Announces Magic Bullet To Zap All Kinds of Killer Viruses

https://www.fastcomp...-killer-viruses