Nicotinamide riboside intervention alleviates hematopoietic system injury of ionizing radiation-induced premature aging mice,Aging Cell

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Nicotinamide riboside intervention alleviates hematopoietic system injury of ionizing radiation-induced premature aging mice
Aging Cell ( IF 8.0 ) Pub Date : 2023-08-31 , DOI: 10.1111/acel.13976
Wenxuan Li ₁ , Xinyue Wang ₁ , Yinping Dong ₁ , Qidong Huo ₁ , Tongpeng Yue ₁ , Xin Wu ₁ , Lu Lu ₁ , Junling Zhang ₁ , Yu Zhao ₁ , Hui Dong ₁ , Deguan Li ₁

Affiliation

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.

中文翻译：

烟酰胺核苷干预减轻电离辐射所致早衰小鼠造血系统损伤

放射治疗会破坏癌细胞，并不可避免地伤害正常人体组织，导致急性辐射暴露（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。本研究采用6 Gy全身照射(TBI)后建立早衰小鼠DEARE模型。评价烟酰胺核苷对早衰小鼠的治疗作用及机制。结果表明，6 Gy TBI 会导致小鼠造血系统过早衰老。烟酰胺核苷治疗通过抑制细胞衰老和改善血清代谢谱来逆转衰老的脾表型。进一步的结果表明，补充烟酰胺核苷可能通过减轻活性氧激活的GCN2/eIF2α/ATF4信号通路来减轻造血干细胞的骨髓偏向并暂时恢复造血干细胞的再生能力。这项研究的结果首先表明，烟酰胺核苷显示出作为辐射暴露人群和接受放射治疗的患者的 DEARE 治疗剂的潜力。

更新日期：2023-08-31

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