Dermal fibroblasts play a role in providing structural support by producing collagen and other structural/support proteins beneath the epidermis. They also produce insulin-like growth factor-1 (IGF-1), which binds to the IGF-1 receptors (IGF-1Rs) on keratinocytes, which further trigger signaling pathways that control cell proliferation and cellular responses to genotoxic stressors like UVB radiation. A recent study determined that the lack of IGF-1 expression resulting from fibroblast senescence in the dermis of geriatric individuals is associated with an augmented incidence of skin cancer. This study tested the hypothesis that pro-energetics creatine monohydrate (Cr) and nicotinamide (NAM) can protect normal dermal human fibroblasts (DHF) against experimentally induced senescence. An experimental model of senescence including primary DHF treated with hydrogen peroxide (H₂O₂) in vitro, with senescence measured by staining for beta-galactosidase activity, p21 protein expression and senescence-associated secretory phenotype cytokine mRNA levels were used. The effect of H₂O₂ on IGF-1 mRNA and protein expression were also determined. The results suggested that pretreatment with Cr or NAM protects DHF from the H₂O₂-induced cell senescence. However, treatment with pro-energetics post-H₂O₂ showed no effect. Furthermore, these agents also impeded reactive oxygen species generation from H₂O₂ treatment. 

Thus, a potential strategy for protecting fibroblasts in geriatric skin from undergoing stress-induced senescence was suggested in this study, which tends to maintain IGF-1 levels, thus limiting carcinogenesis in epidermal keratinocytes.

Source: Mahajan AS, Arikatla VS, Thyagarajan A, et al. Creatine and nicotinamide prevent oxidant-induced senescence in human fibroblasts. Nutrients. 2021;13(11):4102.