Niagen Bioscience, Inc. (NASDAQ: NAGE) has highlighted an independent preclinical study published in Nature Communications that identifies the CD38 enzyme as a primary driver of NAD+ decline in aging placental tissue and finds that nicotinamide riboside (NR) improved pregnancy outcomes in aged mice.

The research, led by a team at Sichuan Agricultural University, measured NAD+ and related metabolites in human placental tissue from younger and older mothers. Older placentas contained lower levels of NAD+, NADH, and NADP+. Higher levels of those metabolites were associated with higher infant birth weight. Similar age-related declines were observed in mice and pigs, suggesting the pattern is not limited to one species.

The study found that CD38-expressing macrophages accumulate in aged placental tissue and deplete NAD+ in neighboring decidual stromal cells. The enzyme acts on NAD+ and NMN outside the cell before they can be used. Because NMN carries a phosphate group that prevents it from crossing the cell membrane directly, it remains exposed to CD38 degradation. Previously published research cited in the press release indicates NR inhibits CD38 activity, which the authors suggest may make NR more effective than NMN in tissues where CD38 is highly active.

In aged pregnant mice, oral NR administration or use of a CD38 inhibitor restored placental NAD+, improved fetal growth, and shifted placental gene expression toward a younger profile.

Niagen Bioscience stated it did not conduct, fund, or design the study, and the NR used was not its proprietary Niagen ingredient. The company is highlighting the research for its relevance to the mechanism of NAD+ decline.

Andrew Shao, PhD, Senior Vice President of Global Scientific and Regulatory Affairs at Niagen Bioscience, said the paper "demonstrated age-related decline in placental tissue NAD+, reaffirmed that CD38 consumes both NAD+ and NMN, and showed the positive reproductive effects of increasing NAD+ with NR." The company noted that additional clinical research is needed to confirm these findings.