Lim Gyeong Min, Cho Gwang-Won
Department of Biological Science, College of Natural Science, Chosun University, 309 Pilmun-daero, Dong-gu, Gwangju 61452, Republic of Korea; BK21 FOUR Education Research Group for Age-Associated Disorder Control Technology, Department of Integrative Biological Science, Chosun University, Gwangju 61452, Republic of Korea.
Department of Biological Science, College of Natural Science, Chosun University, 309 Pilmun-daero, Dong-gu, Gwangju 61452, Republic of Korea; BK21 FOUR Education Research Group for Age-Associated Disorder Control Technology, Department of Integrative Biological Science, Chosun University, Gwangju 61452, Republic of Korea; The Basic Science Institute of Chosun University, Chosun University, Gwangju 61452, Republic of Korea.
Mech Ageing Dev. 2025 Apr;224:112038. doi: 10.1016/j.mad.2025.112038. Epub 2025 Jan 26.
The protective effects of mangiferin (MAG) against etoposide- and high glucose (HG)-induced DNA damage and aging were investigated in human bone marrow-mesenchymal stem cells (hBM-MSCs). Etoposide, a topoisomerase II inhibitor, was used to induce double-strand breaks (DSBs) in hBM-MSCs, resulting in increased genotoxicity, elevated levels of the DNA damage sensor ATM and CDKN1A, and decreased levels of the aging markers H3 and H4. MAG activated AMPK and SIRT1, thus protecting against DSB-induced damage. Following long-term exposure to HG, MAG significantly mitigated DNA damage and delayed cellular aging, as evidenced by the preservation of H3, H4, LMNB1, and SIRT1 mRNA levels and reduction in γ-H2AX foci and DSBs. Furthermore, MAG improved genome stability, as indicated by decreased LINE1 expression and increased levels of the heterochromatin marker TRIM28, thereby maintaining H3K9me3 levels. MAG and metformin treatment enhanced cell proliferation, reduced senescence-associated β-galactosidase staining, and lowered the levels of the senescence-associated secretory phenotype factors IL-1A, IL-1B, IL-6, IL-8, CCL2, and CCL20 and senescence marker CDKN1A, CDKN2A and p53. MAG may reduce DNA damage and delay aging in hBM-MSCs under HG conditions, highlighting their potential as therapeutic agents for aging-related diseases.
在人骨髓间充质干细胞（hBM-MSCs）中研究了芒果苷（MAG）对依托泊苷和高糖（HG）诱导的DNA损伤及衰老的保护作用。依托泊苷是一种拓扑异构酶II抑制剂，用于诱导hBM-MSCs中的双链断裂（DSB），导致遗传毒性增加、DNA损伤传感器ATM和CDKN1A水平升高以及衰老标志物H3和H4水平降低。MAG激活AMPK和SIRT1，从而预防DSB诱导的损伤。长期暴露于HG后，MAG显著减轻DNA损伤并延缓细胞衰老，H3、H4、LMNB1和SIRT1 mRNA水平的保留以及γ-H2AX灶和DSB的减少证明了这一点。此外，MAG改善了基因组稳定性，表现为LINE1表达降低和异染色质标志物TRIM28水平升高，从而维持H3K9me3水平。MAG和二甲双胍治疗增强了细胞增殖，减少了衰老相关β-半乳糖苷酶染色，并降低了衰老相关分泌表型因子IL-1A、IL-1B、IL-6、IL-8、CCL2和CCL20以及衰老标志物CDKN1A、CDKN2A和p53的水平。MAG可能在HG条件下减少hBM-MSCs中的DNA损伤并延缓衰老，突出了它们作为衰老相关疾病治疗剂的潜力。
