Supplementation of Nicotinic Acid and Its Derivatives Up-Regulates Cellular NAD + Level Rather than Nicotinamide Derivatives in Cultured Normal Human Epidermal Keratinocytes

• Published in: Life (Basel, Switzerland) Switzerland), 2024-03, Vol.14 (3), p.413
• Main Authors: Oyama, Takahiro, Yamamoto, Takumi, Kameda, Takeshi, Kamiya, Takanori, Abe, Hideaki, Abe, Takehiko, Tanuma, Sei-Ichi
• Format: Article
• Language: English
• Subjects: Adenine; Amino acids; Antibodies; Biosynthesis; Cell culture; Communication; Energy metabolism; Enzymes; Health aspects; Homeostasis; inflammaging; keratinocyte; Keratinocytes; Mammalian cells; Mammals; Metabolism; Mitochondria; NAD; NAD (Coenzyme); Nervous system diseases; Niacin; Niacinamide; Nicotinamide; Nicotinamide adenine dinucleotide; Nicotinamide phosphoribosyltransferase; Nicotinic acid; Phosphoribosyltransferase; Precursors; Proteins; Reactive oxygen species; rejuvenation; Rotenone; Skin; Superoxide; Superoxide dismutase; Supplements
• ISSN: 2075-1729; 2075-1729
• DOI: 10.3390/life14030413

Nicotinamide adenine dinucleotide (NAD ) plays a pivotal role in various physiological processes within mammalian cells, including energy metabolism, redox homeostasis, and genetic regulation. In the majority of mammalian cellular contexts, NAD biosynthesis primarily relies on vitamin B3, including nicotinamide (NAM) and nicotinic acid (NA). The concept of NAD augmentation therapy has recently emerged as a promising strategy to mitigate aging-associated phenomena, termed rejuvenation. Despite the involvement of diverse enzymatic cascades in NAD biosynthesis, certain cellular environments exhibit deficiencies in specific enzymes, suggesting cell type-dependent variability in optimal NAD precursor selection. However, the optimization of NAD precursors for topical formulations has received scant attention thus far. In the present investigation, we sought to delineate the most efficacious precursor for augmenting NAD levels in human skin keratinocytes. Remarkably, NA supplementation led to a significant 1.3-fold elevation in intracellular NAD levels, even in the presence of nicotinamide phosphoribosyltransferase inhibition by FK866. Additionally, NA mononucleotide demonstrated a 1.5-fold increase (but not significant) in NAD levels following 100 μM application. Conversely, NAM and its derivatives failed to elicit a NAD response in keratinocytes. Notably, NA supplementation elicited up-regulation of mitochondrial superoxide dismutase (SOD2) and sirtuin 3 (SIRT3), indicative of its beneficial impact on mitochondrial function. Furthermore, NA mitigated rotenone-induced mitochondrial reactive oxygen species (ROS) accumulation. Collectively, these findings advocate for the potential utility of NA in topical applications aimed at skin rejuvenation.