Abstract
Nicotinamide (NAM), a NAD+ precursor, is known for its benefits to skin health. Under standard culture conditions, NAM delays the differentiation and enhances the proliferation of human primary keratinocytes (HPKs), leading to the maintenance of stem cells. Here, we investigated the effects of NAM on photoaging in 2D HPK cultures and 3D organotypic epidermal models. In both models, we found that UVB irradiation and hydrogen peroxide induced HPK premature terminal differentiation and senescence. In 3D organotypics, the phenotype was characterized by a thickening of the granular layer expressing filaggrin and loricrin, but thinning of the epidermis overall. NAM limited premature differentiation and ameliorated senescence, as evidenced by the maintenance of lamin B1 levels in both models, with decreased lipofuscin staining and reduced IL-6/IL-8 secretion in 3D models, compared to UVB-only controls. In addition, DNA damage observed after irradiation was accompanied by a decline in energy metabolism, while both effects were partially prevented by NAM. Our data thus highlight the protective effects of NAM against photoaging and oxidative stress in the human epidermis, and pinpoint DNA repair and energy metabolism as crucial underlying mechanisms.
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