Cross-species radioprotection: insights from tardigrade multi-omics

Although the search for appropriate radiation countermeasures has been ongoing for decades, there remains a lack of safe and effective radioprotective pharmaceuticals for preventing, mitigating, or treating acute radiation syndrome (ARS) and other severe radiation injuries, and only a handful of drugs have been approved for clinical use with various side-effects. It has been increasingly recognized that valuable radiation countermeasures can be derived from Earth-based species exhibiting resistance to extremely high levels of ionizing radiation. In the pursuit of the mechanisms that govern radiosensitivity, a groundbreaking study in Science has delved into the radiation tolerance mechanisms of the tardigrade Hypsibius henanensis sp. nov. , revealing cross-species radiation defense strategies by integrating genomics, transcriptomics, and proteomic. Three key findings emerged: The horizontal transfer of the 4,5-DOPA dioxygenase gene from bacteria enhanced antioxidant production. The tardigrade-specific protein TRID1 was crucial for DNA double-strand break repair through liquid-liquid separation. The up-regulation of mitochondrial function-related genes accelerated NAD + regeneration for DNA damage repair. This multi-omics approach not only sheds light on the extraordinary survival strategies of radiotolerant species, but also opens a promising avenue for harnessing cross-species radiation tolerance to develop innovative radioprotective compounds.