Translesion synthesis DNA polymerase gene expression is impacted by age and IGF-1 in epidermal human skin

Geriatric individuals are at an elevated risk of developing skin cancer. Prior studies have shown the skin of older individuals to be slower at removing UV photoproducts from DNA, which suggests that their skin may be more dependent on the use of translesion synthesis (TLS) DNA polymerases to replicate unrepaired UV photolesions. In this work, the expression of TLS DNA polymerases was examined in the epidermis of young adult and geriatric adults. Though significant differences were not observed between 12 young and 12 geriatric adults (study 1), we noted a correlation between increased TLS polymerase expression and lower collagen 1A1 expression among the geriatric samples. Because TLS polymerase expression may be affected by UV radiation, we performed a second study in which we obtained biopsies from young and geriatric adults, exposed the biopsy to UV radiation, and then incubated the biopsies for 24 hours before gene expression analysis. mRNA levels of POLI, POLK, and REV1 were elevated in UVB-irradiated geriatric skin relative to young adult skin. Furthermore, based on prior studies linking low insulin-like growth factor (IGF-1) production with altered responses to UV radiation, we performed work with cultured HaCaT cells in vitro and geriatric skin ex vivo in which we modulated IGF-1 signaling. We found that treatment of HaCaT cells with an IGF-1 receptor antagonist lead to a stronger UVB-dependent induction of several TLS polymerases. Moreover, injection of geriatric skin biopsies with IGF-1 was associated with a reduced UVB-dependent induction of REV1 at the mRNA level. Thus, future studies should consider TLS polymerase expression as a contributor to mutagenesis and skin cancer risk in older adults.