Dermal fibroblasts provide structural support by producing
collagen and other structural/support
proteins beneath the epidermis. Fibroblasts also produce
insulin-like growth factor-1 (IGF-1), which binds to the
IGF-1 receptors (IGF-1Rs) on keratinocytes to activate signaling pathways that regulate cell proliferation and cellular responses to genotoxic stressors like ultraviolet B radiation. Our group has determined that the lack of
IGF-1 expression due to fibroblast senescence in the dermis of geriatric individuals is correlated with an increased incidence of
skin cancer. The present studies tested the hypothesis that pro-energetics
creatine monohydrate (Cr) and
nicotinamide (NAM) can protect normal dermal human fibroblasts (DHF) against experimentally induced senescence. To that end, we used an experimental model of senescence in which primary DHF are 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. We also determined the effect of H2O2 on
IGF-1 mRNA and
protein expression. Our studies indicate that pretreatment with Cr or NAM protects DHF from the H2O2-induced cell senescence. Treatment with pro-energetics post-H2O2 had no effect. Moreover, these agents also inhibited
reactive oxygen species generation from H2O2 treatment. These studies suggest a potential strategy for protecting fibroblasts in geriatric skin from undergoing stress-induced senescence, which may maintain
IGF-1 levels and therefore limit
carcinogenesis in epidermal keratinocytes.