A Summary of a NAD⁺ Metabolism Scientific Review by Covarrubias et al. (2021)

Reviewed by Tamberlyn Blinsink, ND, MPH | Research & Development

Overview

The following summary reviews a scientific narrative examining NAD⁺ metabolism and its roles in multiple cellular processes during ageing. The review, published in Nature Reviews Molecular Cell Biology, covers NAD⁺ biosynthetic and degradative pathways, the consequences of declining NAD⁺ levels on molecular processes relevant to ageing-associated disease, and current preclinical and clinical strategies aimed at restoring NAD⁺ levels.

Summary

NAD⁺ Metabolism and Its Roles in Cellular Processes During Ageing

Published in: Nature Reviews Molecular Cell Biology

Study Design: Narrative scientific review

What Was Reviewed: Covarrubias et al. conducted a comprehensive narrative review of NAD⁺ metabolism with a focus on findings from the five years preceding publication. The authors examined how the primary NAD⁺ biosynthetic pathways—the kynurenine (de novo) pathway, the Preiss–Handler pathway, and the NAM salvage pathway—are regulated during ageing, and how NAD⁺-consuming enzymes including sirtuins, PARPs, CD38, CD157, and SARM1 contribute to the age-related decline in NAD⁺ levels. The review also evaluated how declining NAD⁺ levels influence cellular processes central to ageing biology, including DNA repair and genomic stability, epigenetic regulation, metabolic function, immune cell activity, cellular senescence, and neurodegeneration. Finally, the authors reviewed preclinical data across multiple disease models and summarized ongoing human clinical trials investigating NAD⁺ precursor supplementation—particularly NMN and NR—as well as pharmacological strategies targeting NAD⁺ biosynthetic and degradative enzymes.

About the Reviewer

Name & Title: Tamberlyn Blinsink, Scientific Researcher at Solaray
Credentials: Naturopathic Doctor, Master of Public Health

Bio: Tamberlyn Blinsink, ND, MPH, a licensed naturopath who earned her Doctorate of Naturopathic Medicine from Bastyr University and her Master of Public Health from Purdue University. In addition to her experience in private practice, Dr. Blinsink, ND, MPH is a researcher in the natural products industry. She believes in giving back and has served as a lecturer at continuing education conferences and as a board member at Naturopaths Without Borders and NC Association of Naturopathic Physicians.

Reference

Covarrubias AJ, Perrone R, Grozio A, Verdin E. NAD⁺ metabolism and its roles in cellular processes during ageing. Nat Rev Mol Cell Biol. 2021;22(2):119–141. https://pubmed.ncbi.nlm.nih.gov/33353981/

Back to blog

Frequently Asked Questions

What makes a study “double-blind”?

In double-blind studies, participants and researchers are
both unaware of which participants are in the group taking the active
investigational product and which are part of a control group.

What makes a study “placebo-controlled”?

When studies are placebo-controlled one group takes an active
investigational product and the other group takes an inactive product that has
the same general appearances as the active treatment.

What is a placebo?

Placebos are inactive treatments. Researchers include placebos that have the same general characteristics as an active treatment.

They try to make them indistinguishable from the active treatment regarding
qualities like appearance, taste, and smell.

Why is statistical significance important?

Quality scientific studies look for more than just a numerical difference between treated groups and control groups. These studies also check mathematically for the possibility that any difference between groups might
happen by chance. A difference that is statistically significant is one where the change is not likely to be due to a chance fluctuation within a normal variance.

*These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure or prevent any disease.