Al Nishilli Kamal M, El Zayat Emad M, Abdelgayed Sherein S, Hosney Mohamed, Hassan Nourhan
Department of Biotechnology, Faculty of Science, Cairo University, 12613, Giza, Egypt.
College of Veterinary Medicine, Department of Pathobiology, Tuskegee University, Tuskegee, Alabama, 36088, USA.
Cell Biochem Biophys. 2025 Mar 6. doi: 10.1007/s12013-025-01693-7.
Aging is characterized by a decline in physiological functions and an increased susceptibility to age-related diseases. This study investigates the therapeutic potential of mesenchymal stem cells (MSCs) and pyrroloquinoline quinone (PQQ), individually and in combination, to counteract aging-related physiological declines, with a specific focus on their modulation of the AMP-activated protein kinase (AMPK) pathway, a key regulator of cellular energy homeostasis and stress response. Aging was induced in thirty-seven female rats using D-galactose, simulating the metabolic imbalances and oxidative stress characteristic of aging. The experimental groups included controls, aged rats without treatment, and aged rats treated with MSCs, PQQ, or a combined MSC-PQQ regimen. MSC homing analyses and Behavioral assessments, oxidative stress assays, gene expression profiling, histopathological evaluations were conducted to provide a multidimensional view of treatment efficacy. MSC homing confirmed successful tissue localization and repair, underscoring the regenerative capacity of MSCs. Remarkably, the combined MSC-PQQ therapy (APQQST) markedly improved anxiety-related behaviors, evidenced by increased rearing and grooming activities (p < 0.01). Oxidative stress biomarkers supported these findings; treated groups exhibited significantly reduced malondialdehyde (MDA) levels and elevated antioxidant defenses, including glutathione (GSH) and glutathione peroxidase (GPX) (p < 0.01). Gene expression analysis highlighted the beneficial upregulation of key genes such as LKB1, PFKFB3, TSC2, and HMGR, crucial for cellular energy homeostasis and stress response, with the combination therapy showing the most pronounced effects. Furthermore, histopathological assessments underscored significant liver tissue recovery in treated groups, particularly with combined treatment (APQQST), with minimal vacuolar degeneration and restored hepatic architecture (p < 0.01). These findings highlight the synergistic effects of MSCs and PQQ in mitigating behavioral, molecular, and physiological aspects of aging, underscoring their potential as promising therapeutic agents for promoting healthy aging and offering a foundation for future translational research and clinical applications.
衰老的特征是生理功能下降以及对与年龄相关疾病的易感性增加。本研究调查了间充质干细胞（MSCs）和吡咯喹啉醌（PQQ）单独及联合使用对对抗衰老相关生理衰退的治疗潜力，特别关注它们对AMP激活蛋白激酶（AMPK）途径的调节作用，该途径是细胞能量稳态和应激反应的关键调节因子。使用D-半乳糖诱导37只雌性大鼠衰老，模拟衰老特征性的代谢失衡和氧化应激。实验组包括对照组、未治疗的衰老大鼠以及接受MSCs、PQQ或MSCs-PQQ联合治疗方案的衰老大鼠。进行了MSC归巢分析、行为评估、氧化应激测定、基因表达谱分析、组织病理学评估，以全面了解治疗效果。MSC归巢证实了其成功的组织定位和修复，突出了MSCs的再生能力。值得注意的是，MSCs-PQQ联合疗法（APQQST）显著改善了与焦虑相关的行为，表现为竖毛和理毛活动增加（p<0.01）。氧化应激生物标志物支持了这些发现；治疗组的丙二醛（MDA）水平显著降低，抗氧化防御能力增强，包括谷胱甘肽（GSH）和谷胱甘肽过氧化物酶（GPX）（p<0.01）。基因表达分析突出了关键基因如LKB1、PFKFB3、TSC2和HMGR的有益上调，这些基因对细胞能量稳态和应激反应至关重要，联合治疗显示出最显著的效果。此外，组织病理学评估强调了治疗组肝脏组织的显著恢复，特别是联合治疗（APQQST）组，空泡变性最小，肝结构恢复（p<0.01）。这些发现突出了MSCs和PQQ在减轻衰老的行为、分子和生理方面的协同作用，强调了它们作为促进健康衰老的有前景治疗剂的潜力，并为未来的转化研究和临床应用奠定了基础。
