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Another study showing the downside of NAD+ supplementation.

nad senolytics

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#1 VP.

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Posted 31 May 2019 - 06:23 PM


 This is another study that leads me to beilve Senolytics, not NAD+/NMN is the way to go. I've done one dose of D&Q and only take NMN once a week. https://www.ncbi.nlm...pubmed/31140365

 

Interacting NAD+ and Cell Senescence pathways complicate anti-aging therapies.

During human aging, decrease of NAD+ levels is associated with potentially reversible dysfunction in the liver, kidney, skeletal and cardiac muscle, endothelial cells and neurons. At the same time, the number of senescent cells, associated with damage or stress that secrete pro-inflammatory factors (SASP, Senescence-Associated Secretory Phenotype), increases with age in many key tissues, including the kidneys, lungs, blood vessels, and brain. Senescent cells are believed to contribute to numerous age-associated pathologies and their elimination by senolytic regimens appears to help in numerous preclinical aging-associated disease models including those for atherosclerosis, idiopathic pulmonary fibrosis, diabetes, and osteoarthritis.

A recent report links these processes, such that decreased NAD+ levels associated with aging may attenuate the SASP phenotype potentially reducing its pathological effect. Conversely increasing NAD+ levels by supplementation or genetic manipulation which may benefit tissue homeostasis, also may worsen SASP and encourage tumorigenesis at least in mouse models of cancer. Taken together these findings suggest a fundamental trade-off in treating aging related diseases with drugs or supplements that increase NAD+. Even more interesting is a report that senescent cells can induce CD38 on macrophages and endothelial cells.

In turn increased CD38 expression is believed to be the key modulator of lowered NAD+ levels with aging in mammals. So accumulation of senescent cells may itself be a root cause of decreased NAD+, which in turn could promote dysfunction. On the other hand, the lower NAD+ levels may attenuate SASP, decreasing the pathological influence of senescence.
The elimination of most senescent cells by senolysis before initiating NAD+ therapies may be beneficial and increase safety, and in the best case scenario even eliminate the need for NAD+ supplementation.


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#2 Kevnzworld

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Posted 01 June 2019 - 01:26 AM

Well, as of now all mouse studies with NR and NMN have not demonstrated any increase in cancer, or elevated inflammation ( SASP ). I don’t think it’s an either or proposition. I think the science as of now shows both will ultimately become necessary to extend healthy lifespan. Senolytics and NAD augmentation
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#3 smithx

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Posted 01 June 2019 - 07:40 AM

Eliminating senescent cells first seems like a good policy.

 

Anyone want to re-start the foxo4-DRI group buy?

 

 



#4 male_1978

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Posted 04 June 2019 - 08:32 AM

Another idea could be to not just increase NAD+ alone, but instead add supplements which help consume NAD+ in the way we want it. Like Sirtuin-Activators. So you want have excess NAD+ in your body for long because its used up and does good things.


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#5 Methuselahbones

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Posted 19 June 2019 - 05:56 PM

Another idea could be to not just increase NAD+ alone, but instead add supplements which help consume NAD+ in the way we want it. Like Sirtuin-Activators. So you want have excess NAD+ in your body for long because its used up and does good things.


Interesting, does that mean in the absence of something like that, the increased NAD might not actually be doing anything? I assumed sirtuins functioning in the presence of NAD meant more NAD would compel higher functioning... But I am clearly not a scientist.

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#6 Oakman

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Posted 19 June 2019 - 06:40 PM

Why doesn't this simply reinforce the thought of stopping NAD+ precursors a generous amount of days before starting any intense senolytics and then wait a bit afterwards before starting again. I think it unlikely that one such therapy would remove sufficient inefficient cells and/or CD38 upregulators to make NAD+ precursors unnecessary, esp as you age. In any event, since the science is still fuzzy, a bit more NAD+ can't be bad.







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