CD38 Dictates Age-Related NAD Decline and Mitochondrial Dysfunction through an SIRT3-Dependent Mechanism

David PS

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CD38 Dictates Age-Related NAD Decline and Mitochondrial Dysfunction through an SIRT3-Dependent Mechanism

Highlights
CD38 levels increase in tissues with age and correlate with NAD decline

NAD and mitochondrial function are preserved in old CD38 knockout mice

CD38 metabolizes NMN in vivo and modulates the response to NAD-replacement therapy

fx1.jpg

NAD has a number of potential positive effects in the body.
1-s2.0-S1550413118301220-gr3.jpg

from Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence

Supplement manufacturers have focused on marketing NAD precursors rather than CD38 inhibitors. The NAD precursors are molecules that can be used by cells and tissues to make NAD. They include nicotinamide and vitamin B3 and very expensive alternatives such as nicotinamide riboside (NR) and nicotinamide mono nucleotide (NMN).

CD38 Inhibitors


See the Table at page 26 of this reference.

Quercetin is shown to be a CD38 inhibitor.
 

Nebula

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So 250mg niacinamide with a tablespoon of dried parsley should do the trick.
What’s best for using niacinamide to raise NAD levels? One large dose or spread out? Methylene blue has been the substance I’ve felt increase NAD the most but only a day after a large dose. Not sure why.
 

LeeLemonoil

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So 250mg niacinamide with a tablespoon of dried parsley should do the trick.

No it doesn’t.
If CD38 is overactive (or however you’d call it) supplementing the substrates for NAD+ doesn’t work. Studies, human in vivi studies have proven that.

And dried parsley is certainly not a bad idea. But for having substances that inhibit cd38 in bioavailabile amounts in the tissue where needed is not easily achieved

PARP1-inhibitors like Taurin, Vitamin D and Coffein are useful to help modalste CD38-activity. Vitamin A is a parp1-inhi too but upregulates cd38

And NQO1 is some sort of upstream pathway that has ample data to improve nad+ situation.
That’s where methylene blue works.
And Beta-lapachone
 
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sugarisgreat

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CD38 Dictates Age-Related NAD Decline and Mitochondrial Dysfunction through an SIRT3-Dependent Mechanism

Highlights
CD38 levels increase in tissues with age and correlate with NAD decline

NAD and mitochondrial function are preserved in old CD38 knockout mice

CD38 metabolizes NMN in vivo and modulates the response to NAD-replacement therapy

fx1.jpg

NAD has a number of potential positive effects in the body.
1-s2.0-S1550413118301220-gr3.jpg

from Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence

Supplement manufacturers have focused on marketing NAD precursors rather than CD38 inhibitors. The NAD precursors are molecules that can be used by cells and tissues to make NAD. They include nicotinamide and vitamin B3 and very expensive alternatives such as nicotinamide riboside (NR) and nicotinamide mono nucleotide (NMN).

CD38 Inhibitors


See the Table at page 26 of this reference.

Quercetin is shown to be a CD38 inhibitor.
This is interesting.

CD38 Dictates Age-Related NAD Decline and Mitochondrial Dysfunction through an SIRT3-Dependent Mechanism

Highlights
CD38 levels increase in tissues with age and correlate with NAD decline

NAD and mitochondrial function are preserved in old CD38 knockout mice

CD38 metabolizes NMN in vivo and modulates the response to NAD-replacement therapy

fx1.jpg

NAD has a number of potential positive effects in the body.
1-s2.0-S1550413118301220-gr3.jpg

from Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence

Supplement manufacturers have focused on marketing NAD precursors rather than CD38 inhibitors. The NAD precursors are molecules that can be used by cells and tissues to make NAD. They include nicotinamide and vitamin B3 and very expensive alternatives such as nicotinamide riboside (NR) and nicotinamide mono nucleotide (NMN).

CD38 Inhibitors


See the Table at page 26 of this reference.

Quercetin is shown to be a CD38 inhibitor.
This is interesting. I have tried expensive NAD and noticed nothing.
Any clue how much apigen one should try? 50mg three times a day?
 
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David PS

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This is interesting.

This is interesting. I have tried expensive NAD and noticed nothing.
Any clue how much apigen one should try? 50mg three times a day?

I do not have a clue as to how much is enough. It would seem to depend on your age. The older you are the more one will need to suppress CD38. I have read elsewhere that if you are under 50 years, the NAD boosters may not have any noticeable effects.

Both apigenin and quercetin are in plant foods and so I would think both are bioavailable. I like your idea of dividing the dose. For Covid, I have seen 500mg per day as the recommended dose as part of a larger protocol. I thought 500 mg was a modest amount until I thought about how much food I would need to eat to get 500mg.

I mix 2-4 tablespoons of dried parsley leaves into my yogurt to get my apigenin. I also take 500 mg of quercetin. I have been taking both apigenin and quercetin for over a year. The only change that I noticed was that dental pockets around my teeth disappeared. I have another appt with my periodontist and I am hoping for confirmation that the pockets are still gone. Food sources of apigenin:

Incidentally, there is another thread on the forum that discussed how plain old niacinamide works to increase NAD. So I take that 2x daily as well. I will try to find the link later.

 
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CD38 inhibitor 78c increases mice lifespan and healthspan in a model of chronological aging

Abstract
Nicotinamide adenine dinucleotide (NAD) levels decline during aging, contributing to physical and metabolic dysfunction. The NADase CD38 plays a key role in age-related NAD decline. Whether the inhibition of CD38 increases lifespan is not known. Here, we show that the CD38 inhibitor 78c increases lifespan and healthspan of naturally aged mice. In addition to a 10% increase in median survival, 78c improved exercise performance, endurance, and metabolic function in mice. The effects of 78c were different between sexes. Our study is the first to investigate the effect of CD38 inhibition in naturally aged animals
 
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sugarisgreat

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Thanks for posting. It explains why I always lose weight when I go on vacation. Sunshine everyday (on most vacations).
 
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June 22

CD38 reduces mitochondrial fitness and cytotoxic T cell response against viral infection in lupus patients by suppressing mitophagy​

Here, we report that CD38 reduces CD8+ T cell function by negatively affecting mitochondrial fitness through the inhibition of multiple steps of mitophagy, a process that is critical for mitochondria quality control.
 
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IMPLICATIONS OF THE NADASE CD38 IN COVID PATHOPHYSIOLOGY
Abstract During the COVID-19 pandemic, efforts have been made worldwide to develop effective therapies to address the devastating immune-mediated effects of SARS-CoV-2. With the exception of monoclonal antibody-mediated therapeutics and preventive approaches such as mass immunization, most experimental or repurposed drugs have failed in large randomized clinical trials (https://www.who.int/publications/i/item/therapeutics-and-covid-19- living-guideline). The worldwide spread of SARS-CoV-2 virus revealed specific susceptibilities to the virus among the elderly and individuals with age-related syndromes. These populations were more likely to experience a hyperimmune response characterized by a treatment-resistant acute lung pathology accompanied by multiple organ failure. These observations underscore the interplay between the virus, the biology of aging, and outcomes observed in the most severe cases of SARS-CoV-2 infection. The ectoenzyme CD38 has been implicated in the process of “inflammaging” in aged tissues. In a current publication, Horenstein et al. present evidence to support the hypothesis that CD38 plays a central role in altered immunometabolism resulting from COVID-19 infection. The authors discuss a critical but underappreciated trifecta of CD38-mediated NAD1 metabolism, aging, and COVID-19 immune response and speculate that the CD38/NAD1 axis is a promising therapeutic target for this disease.
 
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Some recent thoughts on CD-38
Previous studies suggested that CD38 plays an important role in the regulation of macrophage function. Therefore, as a new marker of macrophages, the effect of CD38 on macrophage proliferation, polarization and function; its possible mechanism; the relationship between the expression level of CD38 on macrophage surfaces and disease diagnosis, treatment, etc; and the role of targeting CD38 in macrophage-related diseases are reviewed in this paper to provide a theoretical basis for a comprehensive understanding of the relationship between CD38 and macrophages.

CD38: A Significant Regulator of Macrophage Function.

 

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I do not have a clue as to how much is enough. It would seem to depend on your age. The older you are the more one will need to suppress CD38. I have read elsewhere that if you are under 50 years, the NAD boosters may not have any noticeable effects.

Both apigenin and quercetin are in plant foods and so I would think both are bioavailable. I like your idea of dividing the dose. For Covid, I have seen 500mg per day as the recommended dose as part of a larger protocol. I thought 500 mg was a modest amount until I thought about how much food I would need to eat to get 500mg.

I mix 2-4 tablespoons of dried parsley leaves into my yogurt to get my apigenin. I also take 500 mg of quercetin. I have been taking both apigenin and quercetin for over a year. The only change that I noticed was that dental pockets around my teeth disappeared. I have another appt with my periodontist and I am hoping for confirmation that the pockets are still gone. Food sources of apigenin:

Incidentally, there is another thread on the forum that discussed how plain old niacinamide works to increase NAD. So I take that 2x daily as well. I will try to find the link later.

What Quercetin did you purchase? @David PS
 
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What Quercetin did you purchase? @David PS
I settled on Jarrow brand Quercetin. It is sourced from the Japonica Sophora Tree, and is the anhydrous form of quercetin. So it is about 10% more quercetin per gram than dihydrate because two H2O molecules have been removed.
 

sunny

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I settled on Jarrow brand Quercetin. It is sourced from the Japonica Sophora Tree, and is the anhydrous form of quercetin. So it is about 10% more quercetin per gram than dihydrate because two H2O molecules have been removed.
Thank you for that. Will purchase. I appreciate all of your posts, very informative.
 

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