Inhibition of CD38 Increases NAD+ Levels, Extends Life and Healthspan in Mice

CD38 increases as we age, driving down NAD+ levels

CD38 is an enzyme that responds to inflammation, and consumes NAD+. Researchers have long known that CD38 levels increase, and that NAD+ decreases as we age. A 2016 study found that the increased levels of CD38 are a primary driver of decreasing levels of NAD+ (1).

Inhibition of CD38 increases NAD+, extends lifespan and healthspan

Two recent studies have found that inhibition of CD38 (with 78c or PCC1) increase NAD+ levels and result in significant increases in lifespan and healthspan in mice (2, 3)

 “we show that the CD38 inhibitor 78c increases lifespan and healthspan of naturally aged mice.” (2)

“In addition to a 10% increase in median survival, 78c improved exercise performance, endurance, and metabolic function in mice” (2)

“aged mice (2 years old) had lower tissue NAD+ levels, and worse glucose tolerance compared with younger mice. 78c promoted a significant increase in NAD+ levels in tissues of aged mice” (r)

Apigenin inhibits CD38 and increases NAD+

This study found that Apigenin inhibits CD38 levels, leading to increased NAD+ levels,  resulting in numerous health benefits (4)

“Apigenin reduced senescence-associated activity and promoted cell growth”
“Apigenin also increased the activation ratio of silent information regulator 1 (SIRT1), and inhibited CD38 activity in a concentration-dependent manner.”
“Our findings suggest that apigenin is a promising phytochemical for reducing the impact of senescent cells”

Liposomal Apigenin

LIPO Apigenin™  is a sustained-released liposomal delivery system that provides superior absorption of Apigenin in easy-to-swallow capsules.

Our process encapsulates and delivers Apigenin intracellularly in its complete form where it can be absorbed and utilized rather than being destroyed in the stomach.

Decrease inflammation to inhibit CD38 and increase NAD+

CD38 responds to the site of inflammation, which consumes NAD+.  Increased inflammation means more CD38 and  decreased NAD+.

So, in addition to molecules like Apigenin that directly inhibit CD38, there are many natural products that lower systemic inflammation, resulting in lower CD38 and increased NAD+. Some of these are below.

Read more about inflammation effect on NAD+ levels here.

Decrease senescent cells to lower CD38 and increase NAD+ levels

As we age, we accumulate senescent or “zombie” cells, cells that have reached their limit of cell division and would normally be swept away and replaced by younger cells. Instead, these cells hang around and begin to secrete toxins called SASP factors which increase systemic inflammation, one of the hallmarks of aging.

This recent research found that  rising levels of inflammation cause an increase in  CD38, causing systemic NAD+ levels to drop.

“Our data suggest a link between cellular senescence and NAD+ decline in which SASP-mediated upregulation of CD38 can disrupt cellular NAD+ homeostasis.” (5)

Senolytics  such as Fisetin, Quercetin, and Spermidine that target senescent cells lower CD38 and increase NAD+

Multiple pathways to increase NAD+

NAD+ Precursors

Supplemention with NAD+ precursors does increase NAD+ levels, with this new research finding NMN increases NAD+ levels by 300% in humans.

NAD+ Preservers

Limiting consumption of NAD+ by decreasing Inflammation, Senescent cells, and excessive inflammation is a complementary strategy that we highly recommend.

  • Anti-Inflammatories
  • CD38 inhibitors
  • Senolytics

We believe targeting multiple pathways to increase NAD+ is the safest and most effective protocol, so offer products that work well together instead of using a single product.


  1. CD38 dictates age-related NAD decline and mitochondrial dysfunction through a SIRT3-dependent mechanism
  2. CD38 inhibitor 78c increases mice lifespan and healthspan in a model of chronological aging
  3. The flavonoid procyanidin C1 has senotherapeutic activity and increases lifespan in mice
  4. CD38 inhibition by apigenin ameliorates mitochondrial oxidative stress through restoration of the intracellular NAD+/NADH ratio and Sirt3 activity in renal tubular cells in diabetic rats
  5. The NADase CD38 is induced by factors secreted from senescent cells providing a potential link between senescence and age-related cellular NAD+ decline.