How to stop the NAD+ drain

How to stop the NAD+ drain

Strategies to suppress chronic inflammation and sustain NAD+ biosynthesis and circadian function with aging might be effective in maintaining sirtuin activity and possibly robust health. Along these lines, various approaches to address the imbalance in NAD+ synthesis and consumption have been established.

There has been a lot of work examining the potential NAD+ precursor supplementation. There are five major precursors and intermediates to synthesize NAD+: tryptophan, nicotinamide, nicotinic acid, nicotinamide riboside (NR), and nicotinamide mononucleotide (NMN).

In addition, to increase NAD+ levels, activation of the rate-limiting enzyme, NAMPT, has been explored. Small molecule NAMPT activators like SBI-797812 and P7C3 are a pioneering approach to raise intracellular NAD+ and realize its associated salutary effects. NAD+ biosynthesis can be stimulated by the inhibition of an enzyme called ACMSD. Genetic and pharmacological inhibition of ACMSD boosts NAD+ synthesis and SIRT1 activity, ultimately enhancing mitochondrial function. 

Alternatively, NAD+ consumption can be lowered by inhibition of CD38 and PARPs. Several CD38 inhibitors have been discovered, including the naturally occurring apigenin and the small molecule 78c. Olaparib, sold under the brand name Lynparza, is a PARP inhibitor used as a medication for the maintenance treatment of BRCA-mutated advanced ovarian cancer in adults. DSRM-3716 was recently identified as a potent inhibitor of SARM1’s NAD+ consuming activity.

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