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

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/eIF2a/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.

Automated summary

Radiotherapy induces premature aging effects in survivors, but effective methods for preventing this are lacking. This study evaluated the therapeutic effects of nicotinamide riboside on premature aging mice. The results showed that nicotinamide riboside treatment reversed aging phenotypes, improved serum metabolism, and restored the regenerative capacity of hematopoietic stem cells. These findings suggest that nicotinamide riboside has potential as a therapeutic agent for radiation-exposed populations and patients receiving radiotherapy.