Description: In response to ionizing radiation (IR), cells can undergo premature senescence, known as stress-induced senescence, triggered by various stimuli like DNA damage, oxidative stress, and oncogenic activation. Senotherapeutics discovery is crucial for overcoming the obstacle of space radiation in long-duration missions. However, the identification of senescence remains challenging due to a lack of robust biomarkers. Biopico Systems realized that with advancements in organ-on-a-chip technologies, new senotherapeutics can be designed to target specific senescent cell subpopulations. Therefore, Biopico Systems, in collaboration with UC Irvine, is proposing the Platform for Radiation-Induced Senescence using Multiorgans (PRISM) for senotherapeutics screening, to NASA. This platform aims to translate strategies into clinical outcomes for preventing or halting senescence using 3D brain and gut organ models exposed to ionizing radiation. To commercialize the organ platform, Biopico Systems Inc. has filed several patent applications. An alpha prototype of the organ plates and recirculation system has been established, and collaborations are ongoing for drug development. Additionally, there is interest from drug developers developing therapies for neurological diseases, indicating potential customers. The proposal aims to validate organ models for high-throughput senotherapeutics testing, characterize organ models for senescence markers, and screen senescence-modulating interventions for space radiation exposure applications. Apart from NASA's application in radiation countermeasures, health monitoring, and space mission planning, the product will target therapies that induce senescence in cancer cells, potentially slowing down the aging process and extending healthy lifespan, and addressing various age-related diseases such as cardiovascular disease, neurodegenerative disorders, and diabetes.

Benefits: Ionizing radiation presents a significant risk in outer space, particularly for astronauts on long-duration missions such as those to Mars. These missions expose astronauts to substantial heavy ion radiation, which has high linear energy transfer and is considered particularly harmful. During a Mars mission, approximately 30% of an astronaut's cells are estimated to be exposed to radiation for 850 to 1000 days, receiving doses of 0.30 to 0.42 Gy of space radiation. Current spacecraft shielding technology is unable to fully block incoming energetic heavy ion radiation, and these ions are expected to generate additional harmful secondary radiation when interacting with materials. Mitigating radiation-induced senescence is crucial to address accelerated aging and increased susceptibility to age-related diseases among astronauts. Using a multiorgan system to simulate the effects of radiation on different tissues and organs could allow for the screening of senotherapeutics. Space travel is also associated with cognitive decline and neurodegenerative changes. A multiorgan system could model the effects of space radiation on the brain and identify senotherapeutics that could protect or reverse these effects, potentially improving cognitive function in astronauts. Prolonged space travel can also lead to muscle and bone loss, joint stiffness, and pain. A multiorgan system could study the effects of space travel on musculoskeletal health and identify senotherapeutics to preserve muscle and bone mass and improve joint health. Additionally, space travel can weaken the immune system, increasing the risk of infections. A multiorgan system could study the effects of space radiation on the immune system and identify senotherapeutics to boost immune function and protect against infections.Senescence induction therapy can halt the proliferation of cancer cells, potentially leading to their elimination by the immune system. This approach may also address various age-related diseases, including cardiovascular disease, neurodegenerative diseases, and diabetes, by targeting senescent cells. Senescent cells that accumulate in chronic wounds can impair the healing process, but therapies could eliminate these cells and promote faster wound healing. Additionally, senescent cells are implicated in fibrosis, and therapies could potentially reduce fibrosis and improve tissue function. Targeting and eliminating senescent cells could potentially slow down the aging process and extend healthy lifespan. Organ-on-a-chip models can mimic the physiological barriers and functions of organs, allowing for the study of drug absorption, distribution, metabolism, and excretion. These models can provide more accurate and relevant data compared to traditional models, including toxicity studies on specific organs. They can also simulate diseased states, such as cancer, cardiovascular disease, or neurodegenerative disorders, enabling the study of disease mechanisms and screening of potential therapeutics. Screening potential drug candidates for efficacy can help identify promising candidates for further development, including screening existing drugs for new indications, potentially speeding up the drug development process and reducing costs. Overall, the PRISM technology developed in the NASA project has the potential to revolutionize drug screening and development by providing more physiologically relevant models for testing drugs and chemicals