CD38, NAD+ Deficiency, and Senescent Cells
There is a very interesting paper by Judy Campisi and the Buck Institute gang published in the journal Nature Metabolism. The authors tie the enzyme CD38 to the destruction of NAD+, producing the well known NAD+ deficiency that is associated with aging. They also show that it is senescent cells, particularly in body fat, that are largely responsible for inducing production of the CD38 that causes the problem. There's a nice writeup on SingularityHub.com about this work. The clear implication is that we should be doing Fisetin and/or D+Q senolytics along with taking NAD+ booster supplements.
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JGC Thats interesting. I knew about the CD38 and NAD issue but didnt know the source of the CD38. Up until now people have been using CD38 inhibitors like Apigenin.
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D+Q targets senescent cells in adipocytes, so that seems like what you need. Fistein is supposed to target endothelial cells, not sure about adipocytes.
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Fred Cloud I did a bunch of searching and found a reference to fisetin targeting adipocytes too. Now it seems adipocytes and the liver are the two places where M1 macrophage interactions with senescent cells cause the CD38 enzyme to be expressed the most. Long story short; YES, seems like a senolytic treatment before supplementing NAD precursors would be a good move. https://www.sciencedirect.com/science/article/pii/S2352396418303736
I also saw some other work where NAD precursors failed to raise NAD+ levels in those with BMI over 30, which again points to a lot of zombie fat in the body being an issue for NAD+ depletion.
There's even another paper here implicating fisetin in downregulating mTOR!
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