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烟酰胺核糖苷干预可减轻电离辐射诱导的早衰小鼠造血系统损伤。

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

机构信息

Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, China.

出版信息

Aging Cell. 2023 Nov;22(11):e13976. doi: 10.1111/acel.13976. Epub 2023 Aug 31.

DOI:10.1111/acel.13976
PMID:37650560
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10652312/
Abstract

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.

摘要

放疗会破坏癌细胞，不可避免地损害正常人体组织，导致急性辐射暴露的延迟效应（DEARE），并加速大多数幸存者的衰老过程。然而，缺乏预防电离辐射引起的过早衰老的有效方法。在这项研究中，对 6Gy 全身照射（TBI）后的 DEARE 模型过早衰老小鼠进行了建立。然后评估了烟酰胺核苷对过早衰老小鼠的治疗效果和机制。结果表明，6Gy TBI 诱导了小鼠造血系统的过早衰老。烟酰胺核苷治疗通过抑制细胞衰老逆转了衰老脾脏表型，并改善了血清代谢谱。进一步的结果表明，烟酰胺核苷补充缓解了造血干细胞的髓样偏向，并通过减轻活性氧激活的 GCN2/eIF2α/ATF4 信号通路暂时恢复了造血干细胞的再生能力。这项研究的结果首次表明，烟酰胺核苷具有作为辐射暴露人群和接受放疗的患者的 DEARE 治疗剂的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63d0/10652312/3995f708b008/ACEL-22-e13976-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63d0/10652312/89be3f2d559e/ACEL-22-e13976-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63d0/10652312/f0e49c02c35c/ACEL-22-e13976-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63d0/10652312/43b1f7a1413a/ACEL-22-e13976-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63d0/10652312/f6e1219150f7/ACEL-22-e13976-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63d0/10652312/66dcd5a1b88d/ACEL-22-e13976-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63d0/10652312/3995f708b008/ACEL-22-e13976-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63d0/10652312/89be3f2d559e/ACEL-22-e13976-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63d0/10652312/f0e49c02c35c/ACEL-22-e13976-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63d0/10652312/43b1f7a1413a/ACEL-22-e13976-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63d0/10652312/f6e1219150f7/ACEL-22-e13976-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63d0/10652312/66dcd5a1b88d/ACEL-22-e13976-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63d0/10652312/3995f708b008/ACEL-22-e13976-g007.jpg

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