The spaceflight environment poses multiple challenges to homeostasis, including microgravity and ionizing radiation. Together, these factors contribute to cellular stress, and effects include increased generation of reactive oxygen species (ROS), oxidative and DNA damage, cell cycle arrest, and cell senescence. We have shown that a purified diet supplemented with dried plum (DP, 25%) conferred full protection of cancellous structure from the rapid bone loss caused by exposure to ionizing radiation (Schreurs et al., 2016). Based on these promising results for a new countermeasure to prevent space radiation induced-tissue damage, we will conduct additional studies to advance the potential countermeasure to a higher CRL (countermeasure readiness level). We will test the DP diet for its ability to prevent bone loss caused by simulated microgravity as well as exposure to radiation. This will be achieved by exposing mice to each factor (simulated microgravity and radiation) alone and in combination. We hypothesize that spaceflight conditions lead to oxidative damage and bone loss, and that DP, a dietary additive rich in antioxidant and polyphenolic compounds, is an effective countermeasure for multiple tissues, including bone. To achieve these aims, we exposed 16-week-old, C57Bl6/J male mice to different treatments to simulate spaceflight: simulated weightlessness using the well-established Hindlimb-Unloading (HU) system and/or total body irradiation (TBI). Mice were assigned to the following groups: 14 days of normal ambulation (NL) or HU alone, or in combination with total body irradiation, at a dose of 2 Gy 137Cs (0.8G/min). Mice were fed with control diet (CD, AIN93M, Teklad) or AIN93M experimental diet supplemented with DP (25%) 14 days before onset of HU treatment. TBI with 2 Gy 137CS was performed 3 days after onset of HU according to protocols previously shown to cause cancellous bone loss. All groups were sacrificed 14 days after initiating HU. The results analysis are ongoing and will be reported in future reports. Reference Schreurs AS, Shirazi-Fard Y, Shahnazari M, Alwood JS, Truong TA, Tahimic CG, Limoli CL, Turner ND, Halloran B, Globus RK. Dried plum diet protects from bone loss caused by ionizing radiation. Sci Rep. 2016 Feb 11;6:21343.