Nicotinamide Improves Skin Photoaging in Mice by Delaying Cellular Senescence and Suppressing the Senescence-Associated Secretory Phenotype

Nicotinamide (NAM), a precursor of nicotinamide adenine dinucleotide (NAD+), and NAD+ are integral to a variety of cellular processes. NAM supplementation has been shown to have benefits for cellular senescence. However, the mechanism by which NAM improves skin photoaging remains unclear. In this study, the multi-omics analysis revealed that insufficient nicotinamide metabolism may be associated with a decrease in NAD+ synthesis during skin aging. Importantly, we found that NAM has an ameliorating effect on the skin photoaging in mice. Supplementation with NAM restored the expression of the salvage-pathway enzymes and NAD+ consumers. In addition, the supplementation with NAM was shown to restore the expression of skin barrier-related proteins (ZO1 and E-cadherin) and collagen I, while reducing the expression of senescence markers (γ-H2AX, p53, and p21). Furthermore, we found that NAM effectively suppresses the senescence-associated secretory phenotype (SASP) factors’ expression in skin photoaging. Our research reveals the dual role of NAM in attenuating skin photoaging, acting not only to delay cellular senescence but also to suppress the SASP.