β-Nicotinamide mononucleotide blocks UVB-induced collagen reduction via regulation of ROS/MAPK/AP-1 and stimulation of mitochondrial proline biosynthesis.

Abstract

β-Nicotinamide mononucleotide (NMN), as a precursor of long-lived protein co-factor nicotinamide adenine dinucleotide (NAD⁺) in the human body, has demonstrated promising clinical value in treating photoaging and skin wounds. Previous research showed that NMN possessed significant skin protection against UVB-induced photoaging and promoted collagen synthesis. However, its potential mechanism remains unclear. This study aimed to investigate whether NMN improved UVB-induced collagen degradation by regulating ROS/MAPK/AP-1 signaling and stimulating mitochondrial proline biosynthesis. The results showed that NMN notably inhibited UVB-induced ROS production and down-regulated the MAPK/AP-1 signaling pathway. In addition, NMN significantly increased proline levels in mitochondria, which acted as the primary raw materials for collagen synthesis. Further mechanistic analysis revealed that NMN increased the levels of mitochondrial NAD⁺ and NADP(H). Besides, NMN supplementation activated pyrroline-5-carboxylatesynthetase (P5CS), a key enzyme in proline biosynthesis, by increasing SIRT3 levels. However, the promoting effects of NMN on proline and collagen synthesis were significantly inhibited when 3-TYP, a SIRT3 inhibitor, was combined applied. Meanwhile, the effects of NMN on collagen synthesis were reversed when the solute carrier family 25 member 51, a mammalian mitochondrial NAD⁺ transporter, was knocked down. Moreover, animal experiments indicated that NMN ameliorated UVB-induced collagen fiber degradation by activating the SIRT3/P5CS signaling. These results revealed that NMN could combat UVB-induced collagen depletion by regulating the ROS/MAPK/AP-1 and proline synthesis.