Progression of Chronic UVB-Induced Skin Damage During Long-Term Topical Nicotinamide Mononucleotide Treatment in Mice

Nicotinamide mononucleotide (NMN), a precursor of nicotinamide adenine dinucleotide (NAD+), is widely investigated as a potential anti-aging intervention. However, its long-term efficacy and safety, particularly in topical formulations applied to chronically photodamaged skin, remain unclear. This study evaluated whether topical 5% NMN modifies the progression of chronic UVB-induced skin damage in mice. Female C57BL/6NJcl mice were assigned to four groups: non-irradiated control, UVB alone, UVB plus vehicle cream, and UVB plus 5% NMN cream. UVB was delivered to shaved dorsal skin three times weekly at 120 mJ/cm2, and cream was applied after each irradiation through week 25. UVB-exposed groups developed progressive skin damage, with the UVB plus NMN group showing a nonsignificant trend toward greater clinical severity at week 25 (p = 0.08). Histological analysis showed significant increases in epidermal thickness and dysplasia from week 12 to the late endpoint only in the UVB plus NMN group. These changes were accompanied by marked induction of Krt6, Krt16, and S100a8, whereas Krt1 showed no significant change. In contrast, no increase in Parp1 and Sirt1 was observed at the transcriptional level in the NMN group. Parp1 and Sirt1 were significantly upregulated in the UVB alone and UVB plus vehicle groups but not in UVB plus NMN-treated skin. Overall, these findings indicate that long-term topical NMN did not protect chronically UVB-exposed mouse skin and may have contributed to the worsening of photodamage.