10 replies to this topic

[Michael Lustgarten]

NR and NMN are popular ways to try to boost levels of NAD+, but that approach hasn't worked every time in human studies. One reason for that may involve CD38, which degrades both NR and NMN. With the goal of boosting NAD+ levels during aging, why does CD38 increase with age, and what can be done about it?

 

[Oakman]

Flavonoid Apigenin Is an Inhibitor of the NAD+ase CD38

Implications for Cellular NAD+ Metabolism, Protein Acetylation, and Treatment of Metabolic Syndrome

 

CD38 inhibition by quercetin and apigenin increases NAD+ levels in cells.

https://www.ncbi.nlm...les/PMC3609577/

[Neurocryo]

Flavonoid Apigenin Is an Inhibitor of the NAD+ase CD38

Implications for Cellular NAD+ Metabolism, Protein Acetylation, and Treatment of Metabolic Syndrome

 

CD38 inhibition by quercetin and apigenin increases NAD+ levels in cells.

https://www.ncbi.nlm...les/PMC3609577/

 

FWIW I was anecdotally experimenting with this pathway late last year.  When I was on apigenin, quercetin, resveratrol, pterostilbene, niagen 300mg and grape seed extract I had much higher appetite than the same but sans apigenin, quercetin, and resveratrol.

 

My suspicion is my NAD was through the roof with niagen as well as the CD38 inhibition.  It may work for some people but I prefer to allow my body it’s own built in regulation for a powerful supplement in niagen.

[Nate-2004]

After seeing the video of his on inhibitors a few weeks ago I got a few bottles of luteolin from the same company, Swanson, that makes the apigenin I had been using for a few years. I can't say whether it's "better" right now at 47, but if it is that much more of a powerful effect on CD38 it's probably not doing any worse of a job.

[MFRITTMAN]

I add about a half cup of dried parsley to a large salad made from celery and fresh parsley.  The dried parsley alone contains about 700 mg apigenin.  Overall, I may get close to a gram of apigenin per day in my diet.  Dried parsley can be much cheaper source of apigenin than supplements if parsley is purchased in bulk.

[Kentavr]

I see the following sequence:

 

 

1. Defective mitochondria ignite the SASP:

 

https://www.nature.c...1580-020-0228-x

 

2. SASP induces macrophage proliferation and CD38 expression

 

Declining tissue nicotinamide adenine dinucleotide (NAD) levels are linked to ageing and its associated diseases. However, the mechanism for this decline is unclear. Here, we show that pro-inflammatory M1-like macrophages, but not naive or M2 macrophages, accumulate in metabolic tissues, including visceral white adipose tissue and liver, during ageing and acute responses to inflammation. These M1-like macrophages express high levels of the NAD-consuming enzyme CD38 and have enhanced CD38-dependent NADase activity, thereby reducing tissue NAD levels. We also find that senescent cells progressively accumulate in visceral white adipose tissue and liver during ageing and that inflammatory cytokines secreted by senescent cells (the senescence-associated secretory phenotype, SASP) induce macrophages to proliferate and express CD38. These results uncover a new causal link among resident tissue macrophages, cellular senescence and tissue NAD decline during ageing and offer novel therapeutic opportunities to maintain NAD levels during ageing.

 

https://www.ncbi.nlm...les/PMC7908681/

 

3. CD38 hydrolyses NAD+ to NAM and ADP-ribose:

 

https://reactome.org...l/R-HSA-8938076

 

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I have a guess. Defective mitochondria are not only found in senolytic cells. They are also found in ordinary cages.

 

Total SASP = SASP (senescent cells) + SASP (mitochonria not in senescent cells).

 

This may explain why the NAD + level begins to fall until the age of 40, when the number of senescent cells is still small.

 

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We need to break the axis: [defective mitochondria] - [SASP] - [increase in M1 macrophages] - [increase: CD 38 receptors on macrophages M1] - [decrease: NAD +]

 

To reduce the number of defective mitochondria, you can use the property: mitochondria are checked for quality after the division procedure. Defective mitochondria are removed. This procedure must be carried out 15-20 times until the defective mitochondria are almost completely removed.

 

For these purposes, you can use the protocol that Turnbuckle developed. This protocol is on our forum.

 

https://www.longecit...drial-dynamics/

 

 

Edited by Kentavr, 12 August 2021 - 04:36 PM.

[Michael Lustgarten]

Additionally, I see the age-related increase as a contributing factor to increased CD38 expression:

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

 

Which also impairs mitochondrial function:

https://youtu.be/6uQ2YGz_64g?t=1

[Kentavr]

Thank you so much for this video!

 

In my supplements, I did not consider their effect on LPS levels.

 

In the studies of Russian scientists, I found information that inulin, moving through the intestines, like a fishing net, captures E. coli and removes it from the body.

 

This may explain why inulin greatly prolongs the life of mice in the most carefully controlled experiments.

 

Thank you for your information! I didn’t know that E. coli affects NAD + levels so much!

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Additionally, you can search for information on Urolithin A. This supplement has been on sale since May 2021 and is available for purchase.

 

Supplement developers report that this is the only product available as a supplement that activates mitophagy processes. Additionally, they report that Urolithin A reduces intestinal permeability, which can also affect the concentration of E. coli in the blood.

 

 

In this regard, there is speculation that supplementation with Urolithin A may significantly increase NAD + levels.

This may also explain why athletes, taking this supplement in scientific research, feel energized and improve their endurance.

Edited by Kentavr, 13 August 2021 - 03:34 PM.

[Paravani]

I believe that 5-HTP, 5-hydroxytryptophan, is converted to NAD+ as needed.

I believe this on the basis of its molecular relationship to NMN, and also because my hair has turned brown again since February, when I started taking 200mg 5-HTP daily.

Also, a month ago I added 200mg 5-HTP to my husband's daily vitamins, and his beard is now turning brown again, too. He trimmed it today, and the new brown growth is obvious. He's 65, and his beard has been gray for the last 20 years!

We're currently taking 200mg daily -- 100mg morning and night. In a couple of weeks I'll be replacing my morning dose with a 400mg capsule. We'll see then if a higher dose might also rejuvenate my skin.

Edited by Paravani, 16 November 2021 - 02:35 PM.

[Bike_to_120]

Interesting

I had tried NR and NMN early on (not taking anything but metformin and Vit D) and seen no results in blood work or bio metrics.

 Makes sense now.

[Paravani]

I believe that 5-HTP, 5-hydroxytryptophan, is converted to NAD+ as needed.

I believe this on the basis of its molecular relationship to NMN, and also because my hair has turned brown again since February, when I started taking 200mg 5-HTP daily.

Also, a month ago I added 200mg 5-HTP to my husband's daily vitamins, and his beard is now turning brown again, too. He trimmed it today, and the new brown growth is obvious. He's 65, and his beard has been gray for the last 20 years!

We're currently taking 200mg daily -- 100mg morning and night. In a couple of weeks I'll be replacing my morning dose with a 400mg capsule. We'll see then if a higher dose might also rejuvenate my skin.

Just reporting back the results of increasing 5-HTP by 400mg.

The first day I took it, I felt GREAT! But the day after that was a disaster, with a complete emotional breakdown and a crying jag. I knew it was related to the excess 5-HTP though, so I did some research, learned about serotonin poisoning and dopamine suppression, and took some NAC that balanced it out.

No more big increases in 5-HTP. I might still increase it slowly, but am also adding l-dopa and glutamine to my stack to maintain the balance of my neurochemistry. (I don't need to increase B6 or my other B vitamins because I'm already supplementing those sufficiently.)

To whoever marked my previous post as "dangerous and irresponsible" -- If you are a regular here, then you are aware that I'm a newbie. Rather than simply marking my post, it would have been decent to explain to me and any other newbies reading these posts exactly WHAT about my post was dangerous... Because I had no idea of the risk I was taking, and I would very much have appreciated the head's up.

Not warning newbies about dangerous risks in advance is far more irresponsible than newbies proposing supplement increases they aren't aware are dangerous.

Edited by Paravani, 15 December 2021 - 08:03 PM.