The Role of IGF-1 In Geriatric Skin

Keratinocytes are cells that largely occupy the epidermis layer of our skin and function to protect against DNA damage induced by ultraviolet radiation. Keratinocytes rely on the activation of the IGF-1 receptor in order to carry out an appropriate response to UV-B radiation. Keratinocytes themselves do not express the IGF-1 ligand; IGF-1 is produced by fibroblasts found in the dermis layer of the skin. With age, fibroblasts become senescent and this interferes with their ability to produce IGF-1 for the epidermal IGF-1R. This occurrence may aid in understanding why geriatric individuals are at greatest risk for developing nonmelanoma skin cancers, suggesting that age-dependent changes within our skin’s microenvironment are an important key factor. In view of these ideas, three aims were designed for this thesis to further investigate the role of IGF-1 in geriatric skin. Studies have shown that geriatric individuals have lower levels of IGF-1 than younger people. However, there are no current studies that have examined IGF-1 expression among intermediate ages. The first aim investigates more specifically when IGF-1 begins to decrease with age. The second aim seeks to further confirm the improvement of IGF-1 seen in geriatric skin treated with FLR and determine if skin rejuvenation methods have a lasting impact on IGF-1 expression in geriatric individuals. Lastly, the third aim consists of experiments using an IGF-1R inhibitor to treat human skin ex vivo to examine how the deficient IGF-1 signaling impacts the utilization of the potentially mutagenic translesion synthesis pathway of DNA replication following UVB exposure. These studies further define how the age-dependent decline in IGF-1 expression in human skin may impact skin cancer risk