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

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.

The Molecular Mechanisms in Senescent Cells Induced by Natural Aging and Ionizing Radiation

“…Regardless of the inducing stimulus, senescent cells share common mechanisms for activation and maintenance of senescence, which are associated with p53, p21, p16, and pRB proteins [ 2 ]. Li et al [ 184 ] observed increased expression of p-p38, p38, and p16 INK4a proteins in the spleen of irradiated mice. Simultaneously, IR decreases the level of SIRT1, which represses the transcriptional activity of p53 by deacetylation [ 185 ], resulting in increased expression of p53 and p21 CIP1 .…”

“…The dose response of γH2AX foci was analyzed 24 h, 96 h, 1 week, 2 weeks, and 4 weeks after irradiation Residual γH2AX foci persisted in human lymphocytes up to 4 weeks after irradiation [183] HUVECs X-rays 1 or 5 Gy Synchronized G0/G1 phase HUVECs were irradiated with an X-ray dose of 1 or 5 Gy and IRIF were studied from 10 min to 7 days after irradiation By 7 days after irradiation with 5 Gy, the mean number of γH2AX IRIF per nucleus was still significantly more than in unirradiated cells [182] Regardless of the inducing stimulus, senescent cells share common mechanisms for activation and maintenance of senescence, which are associated with p53, p21, p16, and pRB proteins [2]. Li et al [184] observed increased expression of p-p38, p38, and p16 INK4a proteins in the spleen of irradiated mice. Simultaneously, IR decreases the level of SIRT1, which represses the transcriptional activity of p53 by deacetylation [185], resulting in increased expression of p53 and p21 CIP1 .…”