Nicotinamide adenine dinucleotide (NAD) is an important co-factor regulating numerous metabolic enzymes. NAD also serves as a substrate for poly(ADP-ribose) polymerase (PARP) and sirtuins, and regulates various biological processes, such as metabolism, DNA repair, gene expression, and stress responses. In living organisms, a careful balance between NAD production and degradation serves to regulate NAD levels. Recently, a number of studies have demonstrated that NAD levels decline with age, and the deterioration of NAD metabolism promotes aging several aging-associated diseases, including metabolic diseases. Conversely, elevated NAD levels in tissue have been shown to have beneficial effects in both physiological and pathological conditions. Various approaches, such as supplementation with NAD precursors, activation of NAD biosynthetic pathways, and inhibition of NAD degradation, have been used to increase NAD levels in tissue. Nicotinamide riboside (NR) and nicotinamide mononucleotide (NNM) are orally bioavailable NAD+ precursors that have demonstrated beneficial effects against aging and aging-associated diseases in animal models. However, its metabolic pathways in vivo are not fully understood. We developed the method to measure NAD-related metabolites by LC/MS/MS and examined the precise metabolic pathway of NAD precursors. In this seminar, I will present the recent our knowledge about NAD metabolism and its role in aging. I also present the result of clinical study for NMN oral administration.

Reference:

1. Okabe K, Yaku K, Uchida Y, Fukamizu Y, Sato T, Sakurai T, Tobe T, Nakagawa T*. Oral administration of nicotinamide mononucleotide is safe and efficiently increases blood NAD+ levels in healthy subjects. Front Nutr. 9(1): 868640. (2022)
2. Yaku K, Palikhe S, Izumi H, Yoshida T, Hikosaka H, Hayat F, Karim M, Iqbal T, Nitta Y, Sato A, Migaud ME, Ishihara K, Mori H, Nakagawa T*. BST1 regulates nicotinamide riboside metabolism via its glycohydrolase and base-exchange activities. Nat Commun. 12(1): 6767. (2021)
3. Gulshan M, Yaku K, Okabe K, Mahmood A, Sasaki T, Yamamoto M, Hikosaka K, Usui I, Kitamura T, Tobe K, Nakagawa T*. Overexpression of Nmnat3 efficiently increases NAD and NGD levels and ameliorates age-associated insulin resistance. Aging Cell. 17(4): e12798. (2018)
4. Yaku K, Okabe K, Nakagawa T*. Simultaneous Measurement of NAD Metabolome in Aged Mice Tissue Using Liquid Chromatography Tandem-Mass Spectrometry (LC/MS/MS). Biomed Chromatogr. 32(6): e4205. (2018)