Just as NAD decreases with age, CD38 increases as we age. To compound these issues, CD38 is a NADase, which means it reduces our NAD levels. This means that boosting NAD levels is less effective when CD38 is too high. CD38 is inhibited by both Quercetin and Apigenin. 

There are three main applications that use NAD. One relates to sirtuins. Many other genes involved in longevity and health can be activated and deactivated by these genes. Another is an enzyme family known as PARPs that is involved in cellular DNA repair. The third is CD38, a second messenger employed by cells to signal the calcium ion. The most important thing to keep in mind is that there is a limited supply of NAD (if one consuming use is excessively active, it may starve the others).

NAD levels decrease as people age. NAD levels may be roughly half of youthful levels by the time we are in our middle years. As they age, they may plummet much farther. Why do NAD levels decline as we age? While there are several causes, CD38 is a key offender.

As you’ll see in this article, CD38 activity and expression rise with age; by advanced age, it may be several-fold greater in various tissues and cells. Sirtuins, PARPs, and CD38 compete with one another for a limited supply of NAD, so when CD38 uses up too much of it, there is less NAD left over for Sirtuins and PARPs to use. The critical work they conduct suffers as a result. This can be changed by slowing CD38, which increases NAD indirectly and makes more of it available for utilisation by sirtuins and PARPs.

Useful links:

• CD38 dictates age-related NAD decline and mitochondrial dysfunction through a SIRT3-dependent mechanism – PMC
• Flavonoid apigenin is an inhibitor of the NAD+ ase CD38: implications for cellular NAD+ metabolism, protein acetylation, and treatment of metabolic syndrome