Abstract Background: Age is the single greatest risk factor for prostate cancer development. As men pass age 40, their chance of developing prostate cancer increases exponentially each year. The mechanism by which age influences the risk of prostate cancer remains largely unknown, hindering the development of effective preventive approaches. While local events are known to contribute to age-related prostate tumorigenesis, the role of the aging immune system in prostate cancer development has been largely understudied. The aging process affects the adaptive cell-mediated immune response and at the same time there is a shift to a more inflammatory cytokine profile. Recent studies have shown that age-related enhancements of Th17 might contribute to changes in immune function and prostate cancer development. The age-related shift in T-lymphocyte cytokine profile and the enhancement of TH17 generation might be significant contributing factors to the association between age and prostate tumorigenesis. Methods: For our studies we have been using a unique animal model, the glycerol-3-phosphate acyltransferase-1 (GPAT-1) knock out mouse. The GPAT-1 KO young mouse T lymphocyte phenotype mimics old (> 18 m) wild type mice. Preliminary data suggested that cytokines secreted from the GPAT-KO aging mimic T-lymphocytes can promote activation of the STAT3/NF-kB pathways. In order to test if IL-17 was responsible for the strong induction of NF-kB and STAT3, we repeated previous experiments that measured the activation of NF-kB and STAT3, but supplemented the experimental sera and conditioned media with depleting antibodies to IL-17. Successful inhibition of the NF-kB and STAT3 pathways was assessed by Western Blot analysis. Conclusions: Depleting IL-17 in the GPAT-1 KO sera and conditioned media decreased NF-kB activity to the levels of the cells treated with wild-type sera. Sera from the old and GPAT-1 KO mice induced activation of downstream targets of IL-17. These results suggest that circulating factors from the GPAT-1 KO mice mimic those in aging mice and strongly induced signaling pathways involve in the development of prostate cancer. The age-related enhancements of IL-17 may play a key role in prostate cancer initiation and progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5577. doi:10.1158/1538-7445.AM2011-5577