Ginsenoside Rg1 protects against Sca-1+ HSC/HPC cell aging by regulating the SIRT1-FOXO3 and SIRT3-SOD2 signaling pathways in a γ-ray irradiation-induced aging mice model

Aging is characterized by a progressive deterioration in metabolic functions. The present study aimed to investigate the antagonistic effects of ginsenoside Rg1 (Rg1) on the gamma-ray irradiation-induced aging of mixed hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs). C57BL/6 mice were divided into a control group, a gamma-ray irradiation group that served as an aging mouse model, and an Rg1 group. The Rg1 group was treated with Rg1 at dosage of 20 mg/kg/day for 7 days prior to gamma-ray irradiation. The aging mouse model was established by exposing the mice to 6.5-Gy gamma-ray total-body irradiation. Stem cell antigen 1 positive (Sca-1(+)) HSC/HPCs isolated from the mice were examined using a senescence-associated beta-galactosidase (SA-beta-Gal) staining assay. The cell cycle of the HSC/HPCs was examined using flow cytometry. A mixed hematopoietic progenitor cell colony-forming unit (CFU-mix) assay was also conducted. The mRNA and protein expression levels of sirtuin 1 (SIRT1), SIRT3, forkhead box O3 (FOXO3) and superoxide dismutase (SOD2) were evaluated using western blot and reverse transcription-quantitative PCR assays. The results indicated that Rg1 treatment significantly increased white blood cell, red blood cell and platelet counts in peripheral blood compared with those in the gamma-ray irradiation group (P<0.05). However, Rg1 significantly attenuated the senescence of Sca-1(+)HSC/HPCs in the gamma-ray irradiation aging mice model. The proportion of SA-beta-Gal stained HSC/HPCs was significantly decreased and CFU-Mix counts were significantly increased in the Rg1 group compared with the gamma-ray irradiation group (P<0.05). Rg1 significantly increased the mRNA and protein levels of SIRT1, SIRT3, FOXO3 and SOD2 in the Sca-1(+)HSC/HPCs compared with those in the gamma-ray irradiation group (P<0.05). The percentage of Sca-1(+)HSC/HPCs arrested at the G1 phase in the Rg1 group was significantly decreased compared with that in the gamma-ray irradiation group (P<0.05). In conclusion, the present study indicates that Rg1 exerts anti-aging effects via the regulation of SIRT1-FOXO3 and SIRT3-SOD2 signaling pathways, and triggering the progression of Sca-1(+)HSC/HPCs from the G1 phase to the S phase in gamma-ray irradiation-induced aging mice.