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Browsing by Author "Mahajan, Avinash S."
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Item Creatine and Nicotinamide Prevent Oxidant-Induced Senescence in Human Fibroblasts(MDPI, 2021-11-16) Mahajan, Avinash S.; Arikatla, Venkata S.; Thyagarajan, Anita; Zhelay, Tetyana; Sahu, Ravi P.; Kemp, Michael G.; Spandau, Dan F.; Travers, Jeffrey B.; Dermatology, School of MedicineDermal 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.Item Wounding with a Microneedling Device Corrects the Inappropriate Ultraviolet B Radiation Response in Geriatric Ski(SpringerLink, 2020-01) Travers, Jeffrey B.; Kemp, Michael G.; Weir, Nathan M.; Cates, Elizabeth; Alkawar, Abdulrahman M.; Mahajan, Avinash S.; Spandau, Dan F.; Dermatology, School of MedicineNon-melanoma skin cancer primarily affects geriatric patients as evidenced by the fact that only 20% of these cancers are diagnosed in patients under the age of 60 years. Of importance, geriatric skin responds to procarcinogenic ultraviolet B radiation (UVB) in a manner that permits the establishment of tumor cells. Recent studies have indicated that wounding of geriatric skin with fractionated resurfacing lasers and dermabrasion upregulates fibroblast production of insulin-like growth factor-1 (IGF-1) and normalizes the procarcinogenic acute UVB response consisting of basal keratinocytes proliferating while still harboring unrepaired DNA damage. The present studies tested the ability of wounding with a commercially available microneedling device to upregulate IGF-1 levels and normalize the geriatric UVB response. Geriatric volunteers were treated with a microneedling device on buttock skin and 3 months later the IGF-1 levels and UVB responses tested in wounded vs control skin. Wounding via microneedling upregulated IGF-1 and resulted in lower levels of basal keratinocytes proliferating with unrepaired DNA damage. The ability of microneedling to protect against the formation of UVB-damaged proliferating keratinocytes indicates the potential of this wounding modality to reduce aging-associated non-melanoma skin cancer.