放射疗法破坏癌细胞的同时不可避免地损害正常人体组织，引发了迟发性急性辐射暴露（DEARE）的延迟效应，并加速大多数幸存者的衰老过程。然而，缺乏有效的方法来预防电离辐射引起的过早衰老。本研究在6 Gy全身照射（TBI）后建立了DEARE模型老化小鼠。然后评估了尼克酰胺核苷糖对老化小鼠的治疗效果和机制。结果显示，6 Gy TBI诱导了小鼠造血系统的过早衰老。尼克酰胺核苷糖治疗通过抑制细胞衰老改善了脾脏的老化表型，并改善了血清代谢谱。进一步结果表明，尼克酰胺核苷糖补充减轻了造血干细胞的粒形偏向，并通过缓解活化的反应性氧化物GCN2/eIF2α/ATF4信号通路暂时恢复了造血干细胞的再生能力。本研究的结果首次表明，尼克酰胺核苷糖显示了作为DEARE治疗药物的潜力，适用于电离辐射受暴人群和接受放射疗法的患者。© 2023年作者们。《Aging Cell》由解剖学会和约翰威利股份有限公司出版。

Radiotherapy destroys cancer cells and inevitably harms normal human tissues, causing delayed effects of acute radiation exposure (DEARE) and accelerating the aging process in most survivors. However, effective methods for preventing premature aging induced by ionizing radiation are lacking. In this study, the premature aging mice of DEARE model was established after 6 Gy total body irradiation (TBI). Then the therapeutic effects and mechanism of nicotinamide riboside on the premature aging mice were evaluated. The results showed that 6 Gy TBI induced premature aging of the hematopoietic system in mice. Nicotinamide riboside treatment reversed aging spleen phenotypes by inhibiting cellular senescence and ameliorated serum metabolism profiles. Further results demonstrated that nicotinamide riboside supplementation alleviated the myeloid bias of hematopoietic stem cells and temporarily restored the regenerative capacity of hematopoietic stem cells probably by mitigating the reactive oxygen species activated GCN2/eIF2α/ATF4 signaling pathway. The results of this study firstly indicate that nicotinamide riboside shows potential as a DEARE therapeutic agent for radiation-exposed populations and patients who received radiotherapy.© 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.