Identification of the metabolic pathway of “Nicotinamide Riboside (NR)”, an anti-aging nutrient

The research group of Prof. Takashi Nakagawa, Asst. Prof. Keisuke Yaku, and a graduate student Sailesh Palikhe (Department of Molecular and Medical Pharmacology, Faculty of Medicine, University of Toyama) has recently identified the metabolic pathway of orally administered Nicotinamide Riboside (NR) .

NR is one of the forms of vitamin B3 found in the breast milk of mammals such as cow and human. Oral ingestion of NR generates a coenzyme named Nicotinamide Adenine Dinucleotide (NAD+) in body’s cells—an essential molecule that plays important roles in various cellular processes such as energy production, DNA repair, and gene expressions. Additionally, sirtuins, well known as anti-aging molecules, also depend on NAD+ for their enzymatic activities. Recent studies have shown that NAD+ levels decline with age, and this decline further contributes to the aging phenotype and onset of aging-associated diseases. By using as an oral supplement, NR can increase NAD+ levels in tissues and provide protective effects against aging and aging-associated diseases as reported in several animal studies. NR has been also used in human clinical trials for treating various age-associated diseases. However, despite its potential health benefits, the metabolic pathway of orally taken NR was not fully understood.

Prof. Nakagawa research group identified the fate of orally administered NR in mice by using an instrument called mass spectrometer which can accurately measure variety of metabolites. They found that orally ingested NR is degraded in digestive tract by an enzyme called Bone marrow stromal cell antigen 1 (BST1) and is further degraded by gut microbiota. Additionally, the grooup found a novel activity of BST1 in NR metabolism. These results provide important knowledge to advance anti-aging research by using NR as an oral supplement.

Original article information

Title

BST1 regulates nicotinamide riboside metabolism via its glycohydrolase and base-exchange activities

Authors

Keisuke Yaku, Sailesh Palikhe, Hironori Izumi, Tomoyuki Yoshida, Keisuke Hikosaka, Faisal Hayat, Mariam Karim, Tooba Iqbal, Yasuhito Nitta, Atsushi Sato, Marie E Migaud, Katsuhiko Ishihara, Hisashi Mori, Takashi Nakagawa

Journal

Nature Communications. 2021 Nov 19;12(1):6767. doi: 10.1038/s41467-021-27080-3.